Is F3 p.Ile265Val (c.793A>G) pathogenic?

F3 p.Ile265Val (c.793A>G) is classified Uncertain significance in F3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-20). AlphaMissense: likely benign (0.091); Very rare (popmax 0.00267%, afr).

How common is F3 p.Ile265Val (c.793A>G) in the general population?

F3 p.Ile265Val (c.793A>G) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about F3 p.Ile265Val (c.793A>G)?

AlphaMissense predicts likely benign (score 0.091) — an in-silico prediction, not a clinical call.

F3 p.Ile265Val

c.793A>G · rs756710120 · VCV2268370

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.091 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.091	likely benign
REVEL	0.024	moderately benign-leaning
SaProt	LLR -5.93	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 -1.5	GERP -1.1
Overall
CADD	11.16	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 0.00267% African / African-American · 2/74,906 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.00062% 10/1,614,006 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,453
European (non-Finnish)	0.000678%	147,503

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.Ile265Val
Coding: c.793A>G
MANE Select: NM_001993
dbSNP: rs756710120
Type: single nucleotide variant
Location: chr1:94530555 (GRCh38)
Structure: AlphaFold pLDDT 87.29 · 2 PDB
Residue 265: the ig-like c2-type 3 domain; a β-strand

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

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CNTN1 p.Ala668Thr Uncertain significance ★★ ⚠ same type
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CNTN1 p.Ala930Ser Uncertain significance ★★ ⚠ same type
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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-ile265val (accessed [today's date]).

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