# NM_182706.5(SCRIB):c.2025GGA[3] (p.Glu679del)

https://sugi.bio/variant/scrib-p-glu679del

## Summary

**SCRIB p.Glu679del (c.2025GGA[3])** is classified **Likely benign** in SCRIB (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-08-02). Rare (popmax 0.366%, afr); Associated with SCRIB-related disorder.

**At a glance:** Likely benign · review: No assertion criteria · rsID rs761421987 · 1 submitter · 1 linked condition · rare (popmax 0.366%, afr)

## For patients & families {#patients}

This is a change in the SCRIB gene that is classified as likely benign — not considered disease-causing, submitted by 1 submitter, and is linked to SCRIB-related disorder.

*Reference information, not medical advice, and not a prediction for any individual. A genetic counselor or clinician can interpret what it means for you and your family.*

**Support & next steps:** [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [SCRIB](https://sugi.bio/atlas/gene/SCRIB/) |
| Protein change (HGVS p.) | p.Glu679del |
| Coding change (HGVS c.) | c.2025GGA[3] |
| MANE Select transcript | [NM_182706](https://www.ncbi.nlm.nih.gov/nuccore/NM_182706) |
| dbSNP | [rs761421987](https://www.ncbi.nlm.nih.gov/snp/rs761421987/) |
| Variant type | Microsatellite |
| Location | chr8:143808688-143808690 (GRCh38) |
| ClinVar | [VCV3036010](https://www.ncbi.nlm.nih.gov/clinvar/variation/3036010/) |

**All HGVS expressions:** `NC_000008.10:g.144890860CTC[3]`, `NC_000008.11:g.143808690CTC[3]`, `NG_030583.1:g.11681GGA[3]`, `NG_030583.2:g.12074GGA[3]`, `NM_015356.5:c.2025GGA[3]`, `NM_182706.5:c.2025GGA[3]`

## Computational & population evidence {#evidence}

**Concordance:** Mixed / partial computational evidence (see below).

- **Missense predictors (AlphaMissense/REVEL/SaProt) do not apply** to this variant type — they score amino-acid substitutions only. For non-missense variants the computational signal comes from conservation (below), not from a missing predictor score.
- Conservation: phyloP -4.847, GERP -1.57 — fast-evolving / accelerated position
- Molecular consequence: **in-frame indel**.
- CADD: **PHRED 3.069**. No single ClinGen-calibrated threshold exists and the expert panels that use CADD disagree — GUCY2D/AIPL1 require ≥ 20.0 for an untranslated-region variant, ABCA4 ≥ 28.1 for a synonymous or indel variant, the Pulmonary Hypertension panel imports Pejaver 2022's missense-calibrated numbers, and the Antibody Deficiencies panel declines CADD entirely for PIK3CD. CADD v1.7 also incorporates Zoonomia phyloP, so it partly re-expresses the conservation above. *Descriptive; no threshold applied.*
- SpliceAI: **not assessed** — the release is built from a substitutions-only source, so it holds no microsatellite variants. That is a property of the dataset, not of the variant, and is not evidence against a splicing effect.
- Repeat context: **simple_repeat** ((CCT)n, TTCCTCCTCCTCCTC). The alignment of this microsatellite is ambiguous inside a repeating unit, so the same change can be written several ways and a frequency lookup keyed on one representation can miss another. *A qualifier on how reliably this variant can be called and counted — not a pathogenicity signal.*
- Population frequency (gnomAD v4.1): grpmax **0.366%** (afr) · FAF95 0.33% · FAF99 0.316% · 266/72,698 in the highest group · 308/1,544,972 alleles overall — rare (popmax 0.366%, afr).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| African / African-American (grpmax) | 0.366% | 273 |
| Remaining individuals (not grpmax-eligible) | 0.0185% | 5,414 |
| Admixed American | 0.0161% | 6,200 |
| Ashkenazi Jewish (not grpmax-eligible) | 0.00408% | 24,530 |
| South Asian | 0.00255% | 39,182 |
| European (non-Finnish) | 0.00174% | 57,400 |

*Computational predictors are not independent (ClinGen Variant Classification guidance): AlphaMissense (Cheng et al. 2023) carries the ACMG weight for missense and conservation (phyloP/GERP/phastCons) for non-missense; REVEL (Pejaver-2022 calibrated strength bands) and SaProt (Su et al. 2023, structure-aware, ClinVar-independent protein language model, raw LLR) are shown as orthogonal agreement signals, not additive. For frequency, the gnomAD v4.1 grpmax filtering allele frequency (FAF95) is ClinGen's designated BA1/BS1 input (gnomAD v4 guidance v3.0, June 2025); BA1/BS1 thresholds are disease-specific, not a blanket 5%. Predictions, not a clinical determination.*

## Gene constraint & dosage {#gene-context}

**SCRIB** population constraint: LOEUF 0.684, pLI 8.3323e-12, missense-Z -3.2663. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

## Protein context {#protein}

Residue **679** lies in the 'sufficient for targeting to adherens junction and to inhibit cell proliferation' region; the 'disordered' region.

AlphaFold model confidence (whole protein): pLDDT 52.33, 0% of residues very-high.

**42 experimental structure(s)** (PDB): [9KFM](https://www.rcsb.org/structure/9KFM), [9KFN](https://www.rcsb.org/structure/9KFN), [9KFO](https://www.rcsb.org/structure/9KFO), [9KQS](https://www.rcsb.org/structure/9KQS), [9UK1](https://www.rcsb.org/structure/9UK1), [9UK3](https://www.rcsb.org/structure/9UK3) — incl. mutant structure 6EEY.

## What this gene does {#gene-function}

*Describes the biological roles of SCRIB (the gene this variant disrupts) — not effects measured for this specific variant. A damaging variant is expected to affect these functions and pathways; the degree depends on the variant.*

**How this variant is thought to act:** SCRIB's established molecular role includes signaling adaptor activity. p.Glu679del falls in the sufficient for targeting to adherens junction and to inhibit cell proliferation region.


### Pathways affected {#pathways}

SCRIB participates in **6 Reactome pathways** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| [CDC42 GTPase cycle](https://reactome.org/content/detail/R-HSA-9013148) | curated |
| [RHOJ GTPase cycle](https://reactome.org/content/detail/R-HSA-9013409) | curated |
| [RHOQ GTPase cycle](https://reactome.org/content/detail/R-HSA-9013406) | curated |
| [RND2 GTPase cycle](https://reactome.org/content/detail/R-HSA-9696270) | curated |
| [RND3 GTPase cycle](https://reactome.org/content/detail/R-HSA-9696264) | curated |
| [Asymmetric localization of PCP proteins](https://reactome.org/content/detail/R-HSA-4608870) | electronic |

### Molecular function & processes (GO — experimentally supported) {#go}

**Molecular function:** signaling adaptor activity, cadherin binding.

**Biological process:** negative regulation of translational initiation, neural tube closure, positive regulation of receptor recycling, cell population proliferation, cell migration, polarized epithelial cell differentiation.

## Clinical significance {#significance}

**Likely benign** — review status No assertion criteria *(no assertion criteria provided)*, last evaluated 2022-08-02.

**Submitter consensus:** unanimous (1/1 Likely benign).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| PreventionGenetics, part of Exact Sciences | Likely benign | no assertion criteria provided | clinical testing | 2022-08-02 |

## Associated conditions {#conditions}

[SCRIB-related disorder](https://sugi.bio/atlas/disease/scrib-related-disorder/).

**Reported phenotype names (ClinVar):** SCRIB-related disorder, SCRIB-related condition.

## Similar variants {#similar}

Related SCRIB variant pages (same residue, condition, or type): [SCRIB c.3715-19TGCTC[4]](/variant/scrib-c-3715-minus-19tgctc-4), [SCRIB p.Ala796fs](/variant/scrib-p-ala796fs), [SCRIB p.Arg231Gln](/variant/scrib-p-arg231gln), [SCRIB c.2179-10C>T](/variant/scrib-c-2179-minus-10c-t), [SCRIB c.3714+7G>A](/variant/scrib-c-3714-plus-7g-a), [SCRIB c.3910-3dup](/variant/scrib-c-3910-minus-3dup), [SCRIB c.4018-6C>T](/variant/scrib-c-4018-minus-6c-t), [SCRIB c.4514+8C>T](/variant/scrib-c-4514-plus-8c-t).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); gnomAD v4.1 (Broad Institute, built 2026-10-15); AlphaMissense (Cheng et al. 2023, © Google DeepMind — CC BY 4.0, built 2026-01-27); REVEL (Ioannidis et al. 2016 — ODbL, built 2026-07-13); SaProt (Su et al. 2023 — MIT, built 2026-10-14); SpliceAI (Illumina — free for non-commercial use, built 2026-10-13); CADD (Rentzsch et al. 2019, University of Washington — free for non-commercial use, built 2026-10-10); Conservation (phyloP/phastCons/GERP) (UCSC hg38 470-way mammal (Hiller Lab) + Ensembl Compara, built 2026-07-12); gnomAD Non-coding Constraint (Gnocchi) (Chen et al. 2024, Broad Institute — CC0, built 2026-10-11); gnomAD Regional Missense Constraint (Broad Institute — CC0, built 2026-10-13); Pangolin (Zeng & Li 2022 — CC BY 4.0, built 2026-10-11); Repeat regions (UCSC — RepeatMasker, TRF, segmental duplications, built 2026-10-11); ClinGen (ClinGen, built 2026-09-22); UniProt (CC BY 4.0); Reactome / GO (CC BY 4.0, built 2026-09-23); MaveDB (per-record license, built 2026-10-11); CIViC (CC0, built 2026-09-22); Orphanet (Orphanet, built 2026-06-12)

*Primary record: NCBI ClinVar (variation 3036010). Classifications reflect these databases as of the page's build date and may change. Free reference use — not medical advice; consult the primary submitters and a clinician.*