Is F10 p.Ala301Val (c.902C>T) pathogenic?

F10 p.Ala301Val (c.902C>T) is classified Uncertain significance in F10 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-30). AlphaMissense: likely benign (0.0756); Ultra-rare (popmax 0.0165%, mid).

How common is F10 p.Ala301Val (c.902C>T) in the general population?

F10 p.Ala301Val (c.902C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about F10 p.Ala301Val (c.902C>T)?

AlphaMissense predicts likely benign (score 0.0756) — an in-silico prediction, not a clinical call.

F10 p.Ala301Val

c.902C>T · rs145282353 · VCV1707756

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0756 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0756	likely benign
REVEL	0.279	benign-leaning
SaProt	LLR -5.74	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP -2	GERP -3.2
Regional constraint	o/e 0.75	unconstrained · MANE · 10 kb · p 2.9e-09 · regional, not allelic
Overall
CADD	0.303	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 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.00136% 22/1,613,416 alleles · ultra-rare exomes 19/1,461,192 · genomes 3/152,224 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
East Asian	0.00669%	14,957
South Asian	0.00439%	22,769
Remaining individualsnot grpmax-eligible	0.0016%	62,500
African / African-American	0.00133%	75,022
European (non-Finnish)	0.00102%	98,334

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: F10
Protein: p.Ala301Val
Coding: c.902C>T
MANE Select: NM_000504
dbSNP: rs145282353
Type: single nucleotide variant
Location: chr13:113148952 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.47 · 192 PDB
Residue 301: the peptidase s1 domain; a β-strand

Full F10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

F10 p.Glu54Gly Likely pathogenic ★★ same type
F10 p.Gly21Arg Pathogenic ★★ ⚠ same type
F10 p.Gly363Ser Likely pathogenic ★★ same type
F10 p.Gly450Arg Likely pathogenic ★★ same type
F10 p.Arg291Gln Uncertain significance ★★ ⚠ same type
F10 p.Glu268Lys Uncertain significance ★★ ⚠ same type
F10 p.Glu306Lys Uncertain significance ★★ ⚠ same type
F10 p.Gly106= 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/f10-p-ala301val (accessed [today's date]).

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