Is F5 p.Pro1431Ala (c.4291C>G) pathogenic?

F5 p.Pro1431Ala (c.4291C>G) is classified Uncertain significance in F5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-16). AlphaMissense: likely benign (0.0751); Very rare (popmax 0.00424%, nfe); Associated with Inborn genetic diseases.

What condition is associated with F5 p.Pro1431Ala (c.4291C>G)?

F5 p.Pro1431Ala (c.4291C>G) is associated with Inborn genetic diseases, congenital factor V deficiency (ClinVar).

How common is F5 p.Pro1431Ala (c.4291C>G) in the general population?

F5 p.Pro1431Ala (c.4291C>G) is very rare (popmax 0.00424%, nfe) (gnomAD).

What do computational predictors say about F5 p.Pro1431Ala (c.4291C>G)?

AlphaMissense predicts likely benign (score 0.0751) — an in-silico prediction, not a clinical call.

F5 p.Pro1431Ala

c.4291C>G · rs1036528811 · VCV2883587

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0751 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00424%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0751	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	LLR -8.94	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 0.19	GERP 0.69
Regional constraint	o/e 1.08	unconstrained · MANE · 679 bp · p 0.18 · regional, not allelic
Overall
CADD	8.932	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 0.00424% European (non-Finnish) · 50/1,179,996 alleles

Filtering AF 0.00326% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00294%

Overall 0.00322% 52/1,613,908 alleles · very rare exomes 50/1,461,796 · genomes 2/152,112 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00424%	23,600
Remaining individualsnot grpmax-eligible	0.0032%	31,242

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: F5
Protein: p.Pro1431Ala
Coding: c.4291C>G
MANE Select: NM_000130
dbSNP: rs1036528811
Type: single nucleotide variant
Location: chr1:169540799 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.57 · 23 PDB
Residue 1431: the 'b' region; the '35 x 9 aa approximate tandem repeats of [tnp]-l-s-p-d-l-s-q-t' region

Full F5 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

Also linked: congenital factor V deficiency

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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/f5-p-pro1431ala (accessed [today's date]).

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