# NM_006662.3(SRCAP):c.1319del

https://sugi.bio/variant/srcap-c-1319del

## Summary

**SRCAP c.1319del** is classified **Pathogenic** in SRCAP (ClinVar, Single submitter, 1 submitter). No gnomAD frequency available for this variant; Associated with developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities.

**At a glance:** Pathogenic · review: Single submitter · rsID rs2506627905 · 1 submitter · 2 linked conditions · no gnomAD frequency available for this variant

## For patients & families {#patients}

This is a change in the SRCAP gene that is reported as disease-causing, but on limited review, submitted by 1 submitter, and is linked to developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities.

*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 | [SRCAP](https://sugi.bio/atlas/gene/SRCAP/) |
| Coding change (HGVS c.) | c.1319del |
| MANE Select transcript | [NM_006662](https://www.ncbi.nlm.nih.gov/nuccore/NM_006662) |
| dbSNP | [rs2506627905](https://www.ncbi.nlm.nih.gov/snp/rs2506627905/) |
| Variant type | Deletion |
| Location | chr16:30711570-30711570 (GRCh38) |
| ClinVar | [VCV3024229](https://www.ncbi.nlm.nih.gov/clinvar/variation/3024229/) |

**All HGVS expressions:** `NC_000016.10:g.30711571del`, `NC_000016.9:g.30722892del`, `NG_032135.1:g.17431del`, `NG_032135.2:g.17402del`, `NM_006662.3:c.1319del`

## Computational & population evidence {#evidence}

**Concordance:** 1 independent predictor **concordant** with the ClinVar classification.

- **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 11.229, GERP 2.53, phastCons 1 — highly conserved position (PP3-type support)
- Non-coding constraint (Gnocchi): **Z 0.17**, o/e 0.99 (1 kb window 30,711,000–30,712,000). A higher Z means the window carries less variation than expected. Describes the 1 kb window, not this allele. No ClinGen expert panel references Gnocchi and no ACMG-calibrated threshold exists for it. *Descriptive; no cut-point applied.*
- SpliceAI: **not assessed** — the release is built from a substitutions-only source, so it holds no deletion variants. That is a property of the dataset, not of the variant, and is not evidence against a splicing effect.
- Population frequency: **no gnomAD frequency available for this variant** — rarity (ACMG PM2) and BA1/BS1 cannot be assessed for this variant.

*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}

**SRCAP** population constraint: LOEUF 0.223, pLI 1, missense-Z 3.6475; ClinGen dosage — haploinsufficiency 3/3, triplosensitivity 0/3. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

Curated gene–disease validity (ClinGen):

- **Floating-Harbor syndrome** — Definitive (AD)

## Protein context {#protein}


**22 experimental structure(s)** (PDB): [6IGM](https://www.rcsb.org/structure/6IGM), [8X15](https://www.rcsb.org/structure/8X15), [8X19](https://www.rcsb.org/structure/8X19), [8X1C](https://www.rcsb.org/structure/8X1C), [9CA7](https://www.rcsb.org/structure/9CA7), [9CA8](https://www.rcsb.org/structure/9CA8) — incl. mutant structure 9UBD.

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

*Describes the biological roles of SRCAP (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:** SRCAP's established molecular role includes transcription coactivator activity.


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

**Molecular function:** transcription coactivator activity, ATP-dependent chromatin remodeler activity.

**Biological process:** positive regulation of transcription by RNA polymerase II, cAMP/PKA signal transduction.

## Clinical significance {#significance}

**Pathogenic** — review status Single submitter *(criteria provided, single submitter)*.

**Submitter consensus:** unanimous (1/1 Pathogenic).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Molecular Genetics Lab, CHRU Brest | Pathogenic | criteria provided, single submitter | clinical testing |  |

## Associated conditions {#conditions}

[developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities](https://sugi.bio/atlas/disease/developmental-delay-hypotonia-musculoskeletal-defects-and-behavioral-abnormalities/), [Floating-Harbor syndrome](https://sugi.bio/atlas/disease/floating-harbor-syndrome/).

**Reported phenotype names (ClinVar):** Developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities, Floating-Harbor syndrome, Short stature with delayed bone age, expressive language delay, a triangular face with a prominent nose and deep-set eyes, Pelletier-Leisti syndrome, SRCAP-Related Floating-Harbor Syndrome.

## Similar variants {#similar}

Related SRCAP variant pages (same residue, condition, or type): [SRCAP p.Pro2459fs](/variant/srcap-p-pro2459fs), [SRCAP p.Pro2461fs](/variant/srcap-p-pro2461fs), [SRCAP p.Val1012del](/variant/srcap-p-val1012del), [SRCAP c.1187_1228+67del](/variant/srcap-c-1187-1228-plus-67del), [SRCAP c.2298_2300+3del](/variant/srcap-c-2298-2300-plus-3del), [SRCAP p.Ala2262fs](/variant/srcap-p-ala2262fs), [SRCAP p.Arg1897fs](/variant/srcap-p-arg1897fs), [SRCAP p.Gln2517fs](/variant/srcap-p-gln2517fs).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); gnomAD v4.1 (Broad Institute, built 2026-10-14); 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 3024229). 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.*