Is C2CD5 p.Gly642Val (c.1925G>T) pathogenic?

C2CD5 p.Gly642Val (c.1925G>T) is classified Uncertain significance in C2CD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-24). AlphaMissense: ambiguous (0.4329); Rare (popmax 0.1%, mid).

How common is C2CD5 p.Gly642Val (c.1925G>T) in the general population?

C2CD5 p.Gly642Val (c.1925G>T) is rare (popmax 0.1%, mid) (gnomAD).

What do computational predictors say about C2CD5 p.Gly642Val (c.1925G>T)?

AlphaMissense predicts ambiguous (score 0.4329) — an in-silico prediction, not a clinical call.

C2CD5 p.Gly642Val

c.1925G>T · rs534276705 · VCV2359964

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4329 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.1%, mid)

Computational evidence

Protein change
AlphaMissense	0.4329	ambiguous
REVEL	0.367	indeterminate
SaProt	LLR -5.68	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 36 kb · p 0.099 · regional, not allelic
Overall
CADD	27.0	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 0.1% Middle Eastern · 6/6,000 alleles

Filtering AF 0.0435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0297%

Overall 0.0149% 238/1,594,238 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.1%	1,000
European (non-Finnish)	0.0181%	5,538
Remaining individualsnot grpmax-eligible	0.0178%	5,612
Admixed American	0.0155%	6,435
African / African-American	0.00135%	74,042

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: C2CD5
Protein: p.Gly642Val
Coding: c.1925G>T
MANE Select: NM_001286176
dbSNP: rs534276705
Type: single nucleotide variant
Location: chr12:22474869 (GRCh38)
Gene constraint: LOEUF 0.755 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.34
Residue 642: the 'disordered' region

Full C2CD5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C2CD5 p.Ala21Thr Uncertain significance ★ ⚠ same type
C2CD5 p.Ala242Thr Uncertain significance ★ ⚠ same type
C2CD5 p.Ala252Thr Uncertain significance ★ ⚠ same type
C2CD5 p.Ala342Val Uncertain significance ★ ⚠ same type
C2CD5 p.Ala355Thr Uncertain significance ★ ⚠ same type
C2CD5 p.Ala405Val Uncertain significance ★ ⚠ same type
C2CD5 p.Ala433Val Uncertain significance ★ ⚠ same type
C2CD5 p.Ala527Thr 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/c2cd5-p-gly642val (accessed [today's date]).

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