Is C2 p.Arg314Gln (c.941G>A) pathogenic?

C2 p.Arg314Gln (c.941G>A) is classified Uncertain significance in C2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-17). AlphaMissense: likely benign (0.0833); Very rare (popmax 0.00668%, eas).

How common is C2 p.Arg314Gln (c.941G>A) in the general population?

C2 p.Arg314Gln (c.941G>A) is very rare (popmax 0.00668%, eas) (gnomAD).

What do computational predictors say about C2 p.Arg314Gln (c.941G>A)?

AlphaMissense predicts likely benign (score 0.0833) — an in-silico prediction, not a clinical call.

C2 p.Arg314Gln

c.941G>A · rs550498736 · VCV1460531

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0833 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0833	likely benign
REVEL	0.118	moderately benign-leaning
SaProt	LLR -6.15	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 0.59	GERP -2.5, phastCons 0.035
Regional constraint	o/e 0.84	unconstrained · MANE · 18 kb · p 1.1e-06 · regional, not allelic
Overall
CADD	12.92	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% East Asian · 3/44,900 alleles

Filtering AF 0.00199% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00175%

Overall 0.00273% 44/1,612,878 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,967
Admixed American	0.005%	19,996
South Asian	0.00329%	30,361
European (non-Finnish)	0.0028%	35,758
Remaining individualsnot grpmax-eligible	0.0016%	62,476
African / African-American	0.00134%	74,902

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: C2
Protein: p.Arg314Gln
Coding: c.941G>A
MANE Select: NM_000063
dbSNP: rs550498736
Type: single nucleotide variant
Location: chr6:31936014 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.61 · 14 PDB
Residue 314: the vwfa domain; an α-helix

Full C2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C2 p.Arg314Trp Uncertain significance ★★ ⚠ same residue
C2 p.Arg314Gly Uncertain significance ★ ⚠ same residue
ZBTB12 p.Gly314Ala Uncertain significance ★ ⚠ same residue
C2 c.1902+5G>A Uncertain significance ★★ same type
C2 c.2029+5G>A Uncertain significance ★★ same type
C2 p.Ala363Thr Uncertain significance ★★ ⚠ same type
C2 p.Ala682Glu Uncertain significance ★★ ⚠ same type
C2 p.Arg124Gln 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/c2-p-arg314gln (accessed [today's date]).

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