Is C2CD3 p.Val2163Phe (c.6487G>T) pathogenic?

C2CD3 p.Val2163Phe (c.6487G>T) is classified Likely benign in C2CD3 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-06). AlphaMissense: likely benign (0.084); Rare (popmax 0.33%, sas).

How common is C2CD3 p.Val2163Phe (c.6487G>T) in the general population?

C2CD3 p.Val2163Phe (c.6487G>T) is rare (popmax 0.33%, sas) (gnomAD).

What do computational predictors say about C2CD3 p.Val2163Phe (c.6487G>T)?

AlphaMissense predicts likely benign (score 0.084) — an in-silico prediction, not a clinical call.

C2CD3 p.Val2163Phe

c.6487G>T · rs550167325 · VCV1658277

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.084 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.33%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.084	likely benign
REVEL	0.028	moderately benign-leaning
SaProt	LLR -7.85	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.84	GERP -2.3
Regional constraint	o/e 0.92	unconstrained · MANE · 157 kb · p 9.8e-06 · regional, not allelic
Overall
CADD	0.566	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 0.33% South Asian · 277/84,058 alleles

Filtering AF 0.298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.285%

Overall 0.108% 1,654/1,536,232 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.33%	303
Admixed American	0.133%	750
Remaining individualsnot grpmax-eligible	0.125%	801
European (non-Finnish)	0.105%	948
Middle Eastern	0.0501%	1,996
African / African-American	0.0219%	4,571
Finnishnot grpmax-eligible	0.00672%	14,876
East Asian	0.00489%	20,454

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.Val2163Phe
Coding: c.6487G>T
MANE Select: NM_001286577
dbSNP: rs550167325
Type: single nucleotide variant
Location: chr11:74033673 (GRCh38)
Gene constraint: LOEUF 0.637 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.65
Residue 2163: the 'disordered' region

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

Similar variants

C2CD3 p.Val2163= Benign ★ same residue
C2CD3 c.3911-2A>T Pathogenic/Likely pathogenic ★★ same type
C2CD3 p.Arg621Ter Pathogenic/Likely pathogenic ★★ same type
C2CD3 p.Arg666Ter Pathogenic ★★ same type
C2CD3 p.Arg768Ter Pathogenic/Likely pathogenic ★★ same type
C2CD3 p.Tyr173Ter Pathogenic/Likely pathogenic ★★ same type
C2CD3 c.2085+5G>A Uncertain significance ★★ same type
C2CD3 c.4951+6C>T 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/c2cd3-p-val2163phe (accessed [today's date]).

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