# NM_001039374.5(CCDC183):c.272T>A (p.Val91Glu)

https://sugi.bio/variant/ccdc183-p-val91glu

## Summary

**CCDC183 p.Val91Glu (c.272T>A)** is classified **Likely benign** in CCDC183 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-01). AlphaMissense: likely benign (0.2035); Rare (popmax 0.315%, nfe).

**At a glance:** Likely benign · review: Single submitter · 1 submitter · AlphaMissense likely benign · rare (popmax 0.315%, nfe)

## For patients & families {#patients}

This is a change in the CCDC183 gene that is classified as likely benign — not considered disease-causing, submitted by 1 submitter.

*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 | [CCDC183](https://sugi.bio/atlas/gene/CCDC183/) |
| Protein change (HGVS p.) | p.Val91Glu |
| Coding change (HGVS c.) | c.272T>A |
| MANE Select transcript | [NM_001039374](https://www.ncbi.nlm.nih.gov/nuccore/NM_001039374) |
| Variant type | single nucleotide variant |
| Location | chr9:136800003-136800003 (GRCh38) |
| ClinVar | [VCV4083775](https://www.ncbi.nlm.nih.gov/clinvar/variation/4083775/) |

**All HGVS expressions:** `NC_000009.11:g.139694455T>A`, `NC_000009.12:g.136800003T>A`, `NG_118328.1:g.563T>A`, `NG_118328.2:g.563T>A`, `NM_001039374.5:c.272T>A`

## Computational & population evidence {#evidence}

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

- AlphaMissense **likely benign** (0.2035)
- REVEL 0.098 (moderately benign-leaning) — agrees with AlphaMissense
- SaProt LLR -3.325 (tolerated) — agrees with AlphaMissense
- → **In-silico consensus:** AlphaMissense, REVEL and SaProt all call this tolerated
- SpliceAI predicts **acceptor gain** (Δ 0.23) — a splice-altering prediction the current classification does not reflect
- Conservation: phyloP -0.932, GERP -2.3, phastCons 0.011 — not a conserved position (phyloP < 0.1, ACGS BP7 cut)
- CADD: **PHRED 21.1**. 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.*
- Regional missense constraint: **o/e 1.12** across the covering region of the MANE Select transcript (136,796,398–136,807,687), spanning 11,289 bp. Chi-square p 0.0024. Describes the region, not this allele; gnomAD v4.1.1's own constrained determination. *Descriptive; no ACMG code applied.*
- SpliceAI deltas (raw): acceptor loss **0.10**, donor loss **0.00**, acceptor gain **0.23**, donor gain **0.00**. Largest is acceptor gain.
- SpliceAI deltas (masked): acceptor loss **0.00**, donor loss **0.00**, acceptor gain **0.23**, donor gain **0.00**.
- Pangolin: Δ**0.26** (loss), gain 0.08 / loss 0.26. SpliceAI calls gain. An independent predictor to SpliceAI — a different model trained on different data. *Descriptive; ClinGen's SVI calibration covers SpliceAI, not Pangolin, so no ACMG code is assigned.*
- Population frequency (gnomAD v4.1): grpmax **0.315%** (nfe) · FAF95 0.307% · FAF99 0.303% · 3,677/1,166,908 in the highest group · 4,954/1,585,708 alleles overall — rare (popmax 0.315%, nfe).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| Ashkenazi Jewish (not grpmax-eligible) | 1.8% | 56 |
| Remaining individuals (not grpmax-eligible) | 0.428% | 233 |
| European (non-Finnish) (grpmax) | 0.315% | 317 |
| South Asian | 0.253% | 395 |
| Finnish (not grpmax-eligible) | 0.213% | 469 |
| Middle Eastern | 0.189% | 530 |
| Admixed American | 0.188% | 531 |
| African / African-American | 0.0348% | 2,870 |

Ashkenazi Jewish shows a higher raw frequency than the grpmax group. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and "Remaining individuals" — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

*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}

**CCDC183** population constraint: LOEUF 1.225, pLI 7.1871e-23, missense-Z -1.4154. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 81.98, 49% of residues very-high.

## Clinical significance {#significance}

**Likely benign** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2026-01-01.

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

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| CeGaT Center for Human Genetics Tuebingen | Likely benign | criteria provided, single submitter | clinical testing | 2026-01-01 |

**Reported phenotype names (ClinVar):** not provided, none provided.

## Similar variants {#similar}

Related CCDC183 variant pages (same residue, condition, or type): [CCDC183 p.Val91fs](/variant/ccdc183-p-val91fs), [CCDC183 p.Gln296Ter](/variant/ccdc183-p-gln296ter), [CCDC183 p.Ala238Thr](/variant/ccdc183-p-ala238thr), [CCDC183 p.Ala348Thr](/variant/ccdc183-p-ala348thr), [CCDC183 p.Ala392Val](/variant/ccdc183-p-ala392val), [CCDC183 p.Ala424Glu](/variant/ccdc183-p-ala424glu), [CCDC183 p.Ala518Thr](/variant/ccdc183-p-ala518thr), [CCDC183 p.Arg117Pro](/variant/ccdc183-p-arg117pro).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-11); gnomAD v4.1 (Broad Institute, built 2026-10-06); 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 2026-07-14); 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 4083775). 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.*