Is C7 p.Ser231Tyr (c.692C>A) pathogenic?

C7 p.Ser231Tyr (c.692C>A) is classified Uncertain significance in C7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-19). AlphaMissense: likely benign (0.0921); Very rare (popmax 0.00669%, afr).

How common is C7 p.Ser231Tyr (c.692C>A) in the general population?

C7 p.Ser231Tyr (c.692C>A) is very rare (popmax 0.00669%, afr) (gnomAD).

What do computational predictors say about C7 p.Ser231Tyr (c.692C>A)?

AlphaMissense predicts likely benign (score 0.0921) — an in-silico prediction, not a clinical call.

C7 p.Ser231Tyr

c.692C>A · rs183261438 · VCV1938362

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0921 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00669%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0921	likely benign
REVEL	0.298	indeterminate
SaProt	LLR -9.22	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.4	GERP -3.6
Overall
CADD	1.267	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 0.00669% African / African-American · 5/74,742 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.000311% 5/1,609,476 alleles · very rare

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: C7
Protein: p.Ser231Tyr
Coding: c.692C>A
MANE Select: NM_001565 · reported on NM_000587
dbSNP: rs183261438
Type: single nucleotide variant
Location: chr5:40945322 (GRCh38)
Structure: AlphaFold pLDDT 89.67 · 6 PDB

Full C7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C7 p.Ser231Cys Benign ★★ ⚠ same residue
C7 c.281-1G>T Pathogenic/Likely pathogenic ★★ same type
C7 c.63-1G>A Pathogenic ★★ same type
C7 c.739-2A>G Likely pathogenic ★★ same type
C7 p.Arg402Ter Pathogenic/Likely pathogenic ★★ same type
C7 p.Gln271Ter Pathogenic/Likely pathogenic ★★ same type
C7 p.Gly379Arg Pathogenic/Likely pathogenic ★★ ⚠ same type
C7 p.Trp205Ter Pathogenic/Likely pathogenic ★★ 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/c7-p-ser231tyr (accessed [today's date]).

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