Is CCDC183 p.Val91Glu (c.272T>A) pathogenic?

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).

How common is CCDC183 p.Val91Glu (c.272T>A) in the general population?

CCDC183 p.Val91Glu (c.272T>A) is rare (popmax 0.315%, nfe) (gnomAD).

What do computational predictors say about CCDC183 p.Val91Glu (c.272T>A)?

AlphaMissense predicts likely benign (score 0.2035) — an in-silico prediction, not a clinical call.

CCDC183 p.Val91Glu

c.272T>A · VCV4083775

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2035 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.315%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2035	likely benign
REVEL	0.098	moderately benign-leaning
SaProt	LLR -3.33	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.23	acceptor gain · deltas
Pangolin	Δ0.26	loss · gain 0.08 · SpliceAI calls gain · independent
Constraint at this position
Conservation	phyloP -0.93	GERP -2.3, phastCons 0.011
Regional constraint	o/e 1.12	unconstrained · MANE · 11 kb · p 0.0024 · regional, not allelic
Overall
CADD	21.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.315% European (non-Finnish) · 3,677/1,166,908 alleles

Filtering AF 0.307% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.303%

Overall 0.312% 4,954/1,585,708 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.8%	56
Remaining individualsnot grpmax-eligible	0.428%	233
European (non-Finnish)grpmax	0.315%	317
South Asian	0.253%	395
Finnishnot 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 above it. 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.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CCDC183
Protein: p.Val91Glu
Coding: c.272T>A
MANE Select: NM_001039374
Type: single nucleotide variant
Location: chr9:136800003 (GRCh38)
Gene constraint: LOEUF 1.225 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.98

Full CCDC183 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC183 p.Val91fs Likely benign ★ same residue
CCDC183 p.Gln296Ter Likely pathogenic ★ same type
CCDC183 p.Ala238Thr Uncertain significance ★ ⚠ same type
CCDC183 p.Ala348Thr Uncertain significance ★ ⚠ same type
CCDC183 p.Ala392Val Uncertain significance ★ ⚠ same type
CCDC183 p.Ala424Glu Uncertain significance ★ ⚠ same type
CCDC183 p.Ala518Thr Uncertain significance ★ ⚠ same type
CCDC183 p.Arg117Pro Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ccdc183-p-val91glu (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown