Is F7 p.Cys232Ser (c.695G>C) pathogenic?

F7 p.Cys232Ser (c.695G>C) is classified Uncertain significance in F7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-30). AlphaMissense: likely pathogenic (0.9902); Very rare (popmax 0.00133%, afr); Associated with Inborn genetic diseases.

What condition is associated with F7 p.Cys232Ser (c.695G>C)?

F7 p.Cys232Ser (c.695G>C) is associated with Inborn genetic diseases (ClinVar).

How common is F7 p.Cys232Ser (c.695G>C) in the general population?

F7 p.Cys232Ser (c.695G>C) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about F7 p.Cys232Ser (c.695G>C)?

AlphaMissense predicts likely pathogenic (score 0.9902) — an in-silico prediction, not a clinical call.

F7 p.Cys232Ser

c.695G>C · VCV4252400

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9902 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9902	likely pathogenic · top 1% in F7
REVEL	0.865	moderately pathogenic-leaning
SaProt	LLR -12.91	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 13 kb · p 0.22 · regional, not allelic
Overall
CADD	26.6	PHRED · no single calibrated threshold — expert panels disagree

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

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM C254S vs ClinVar C232S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,942 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00031% 5/1,614,028 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,942
European (non-Finnish)	0.000339%	295,006

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: F7
Protein: p.Cys232Ser
Coding: c.695G>C
MANE Select: NM_019616
Type: single nucleotide variant
Location: chr13:113117552 (GRCh38)
Gene constraint: LOEUF 1.113 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 82.64 · 114 PDB
Residue 232: a β-strand; a disulfide bond; the peptidase s1 domain

Full F7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

F7 p.Cys232Arg Uncertain significance ★ ⚠ same residue
F7 p.Arg434His Uncertain significance ★★ ⚠ same condition
F7 p.Asp234Asn Uncertain significance ★★ ⚠ same condition
F7 p.Glu27Lys Uncertain significance ★★ ⚠ same condition
F7 p.His30Tyr Uncertain significance ★★ ⚠ same condition
F7 p.Lys147Arg Uncertain significance ★★ ⚠ same condition
F7 p.Thr345Ser Uncertain significance ★★ ⚠ same condition
F7 p.Trp225Cys Uncertain significance ★★ ⚠ same condition

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/f7-p-cys232ser (accessed [today's date]).

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