Is F3 p.Arg232Gln (c.695G>A) pathogenic?

F3 p.Arg232Gln (c.695G>A) is classified Likely benign in F3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-09). AlphaMissense: likely benign (0.0672); Ultra-rare (popmax 0.0533%, amr).

How common is F3 p.Arg232Gln (c.695G>A) in the general population?

F3 p.Arg232Gln (c.695G>A) is ultra-rare (popmax 0.0533%, amr) (gnomAD).

What do computational predictors say about F3 p.Arg232Gln (c.695G>A)?

AlphaMissense predicts likely benign (score 0.0672) — an in-silico prediction, not a clinical call.

F3 p.Arg232Gln

c.695G>A · VCV3276966

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0672 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0533%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0672	likely benign
REVEL	0.017	moderately benign-leaning
SaProt	LLR -4.87	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 0.15	GERP -3.1, phastCons 0.022
Regional constraint	o/e 0.97	unconstrained · MANE · 11 kb · p 0.63 · regional, not allelic
Overall
CADD	1.545	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 0.0533% Admixed American · 32/60,004 alleles

Filtering AF 0.0387% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0339%

Overall 0.00248% 40/1,614,038 alleles · ultra-rare exomes 35/1,461,884 · genomes 5/152,154 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0533%	1,875
South Asian	0.00439%	22,772
East Asian	0.00223%	44,864
Remaining individualsnot grpmax-eligible	0.0016%	62,490
African / African-American	0.00133%	74,922
European (non-Finnish)	8.47e-05%	1,180,036

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: F3
Protein: p.Arg232Gln
Coding: c.695G>A
MANE Select: NM_001993
Type: single nucleotide variant
Location: chr1:94532377 (GRCh38)
Gene constraint: LOEUF 0.839 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.40 · 54 PDB

Full F3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

F3 p.Arg163Trp Benign ★★ ⚠ same type
F3 p.Gly281Glu Benign ★★ same type
F3 p.Thr36Ala Benign ★★ same type
F3 p.Ala17Thr Uncertain significance ★ ⚠ same type
F3 p.Ala30Thr Uncertain significance ★ ⚠ same type
F3 p.Arg11His Uncertain significance ★ ⚠ same type
F3 p.Arg176Trp Uncertain significance ★ same type
F3 p.Arg228Gln 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/f3-p-arg232gln (accessed [today's date]).

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