Is C2CD3 p.Pro773Arg (c.2318C>G) pathogenic?

C2CD3 p.Pro773Arg (c.2318C>G) is classified Benign in C2CD3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.1038); Common (popmax 9.28%, eas) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about C2CD3 p.Pro773Arg (c.2318C>G)?

AlphaMissense predicts likely benign (score 0.1038) — an in-silico prediction, not a clinical call.

C2CD3 p.Pro773Arg

Q: How common is C2CD3 p.Pro773Arg (c.2318C>G) in the general population?

C2CD3 p.Pro773Arg (c.2318C>G) is common (popmax 9.28%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2318C>G · rs34050666 · VCV1552012

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1038 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 9.28%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1038	likely benign
REVEL	0.089	moderately benign-leaning
SaProt	LLR -7.37	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 2.6	GERP 0.86, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 157 kb · p 9.8e-06 · regional, not allelic
Overall
CADD	20.8	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 9.28% East Asian · 4,165/44,878 alleles

Filtering AF 9.05% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.95%

Overall 1.57% 25,352/1,614,178 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	9.28%	11
South Asian	1.98%	50
Finnishnot grpmax-eligible	1.96%	51
Remaining individualsnot grpmax-eligible	1.62%	62
Admixed American	1.58%	63
Ashkenazi Jewishnot grpmax-eligible	1.36%	73
European (non-Finnish)	1.31%	76
Middle Eastern	1.29%	78
African / African-American	0.24%	417
Amishnot grpmax-eligible	0.219%	456

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.Pro773Arg
Coding: c.2318C>G
MANE Select: NM_001286577
dbSNP: rs34050666
Type: single nucleotide variant
Location: chr11:74103393 (GRCh38)
Gene constraint: LOEUF 0.637 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.65
Residue 773: a UniProt-annotated variant site (in)

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

Similar variants

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
C2CD3 c.5495+4A>G 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-pro773arg (accessed [today's date]).

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