Is C2CD3 p.Val926Ala (c.2777T>C) pathogenic?

C2CD3 p.Val926Ala (c.2777T>C) is classified Benign/Likely benign in C2CD3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-06). AlphaMissense: likely pathogenic (0.7769); Rare (popmax 0.323%, sas); Associated with Inborn genetic diseases.

What condition is associated with C2CD3 p.Val926Ala (c.2777T>C)?

C2CD3 p.Val926Ala (c.2777T>C) is associated with Inborn genetic diseases (ClinVar).

How common is C2CD3 p.Val926Ala (c.2777T>C) in the general population?

C2CD3 p.Val926Ala (c.2777T>C) is rare (popmax 0.323%, sas) (gnomAD).

What do computational predictors say about C2CD3 p.Val926Ala (c.2777T>C)?

AlphaMissense predicts likely pathogenic (score 0.7769) — an in-silico prediction, not a clinical call.

C2CD3 p.Val926Ala

c.2777T>C · rs564676965 · VCV1619333

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.7769 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.323%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7769	likely pathogenic · top 10% in C2CD3
REVEL	0.478	indeterminate
SaProt	LLR -7.38	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 157 kb · p 9.8e-06 · regional, not allelic
Overall
CADD	25.8	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 0.323% South Asian · 294/91,086 alleles

Filtering AF 0.292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.281%

Overall 0.0191% 309/1,614,082 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.323%	310
Remaining individualsnot grpmax-eligible	0.0192%	5,208
African / African-American	0.00133%	75,060
European (non-Finnish)	0.00017%	589,957

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: C2CD3
Protein: p.Val926Ala
Coding: c.2777T>C
MANE Select: NM_001286577
dbSNP: rs564676965
Type: single nucleotide variant
Location: chr11:74098211 (GRCh38)
Gene constraint: LOEUF 0.637 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.65

Full C2CD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

C2CD3 c.2085+5G>A Uncertain significance ★★ same condition
C2CD3 c.4951+6C>T Uncertain significance ★★ same condition
C2CD3 p.Ala1382Pro Uncertain significance ★★ ⚠ same condition
C2CD3 p.Ala1777Thr Uncertain significance ★★ ⚠ same condition
C2CD3 p.Ala95Thr Uncertain significance ★★ ⚠ same condition
C2CD3 p.Arg1122Ile Uncertain significance ★★ ⚠ same condition
C2CD3 p.Arg1145His Uncertain significance ★★ ⚠ same condition
C2CD3 p.Arg1183His Uncertain significance ★★ ⚠ same condition

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/c2cd3-p-val926ala (accessed [today's date]).

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