Is F5 p.Val394Ala (c.1181T>C) pathogenic?

F5 p.Val394Ala (c.1181T>C) is classified Conflicting classifications of pathogenicity in F5 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-01-11). AlphaMissense: ambiguous (0.4763); Ultra-rare (popmax 0.0747%, afr); Associated with congenital factor V deficiency.

What condition is associated with F5 p.Val394Ala (c.1181T>C)?

F5 p.Val394Ala (c.1181T>C) is associated with congenital factor V deficiency (ClinVar).

How common is F5 p.Val394Ala (c.1181T>C) in the general population?

F5 p.Val394Ala (c.1181T>C) is ultra-rare (popmax 0.0747%, afr) (gnomAD).

How is Congenital factor V deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about F5 p.Val394Ala (c.1181T>C)?

AlphaMissense predicts ambiguous (score 0.4763) — an in-silico prediction, not a clinical call.

F5 p.Val394Ala

c.1181T>C · rs142875000 · VCV1084788

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4763 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0747%, afr)

Conditions

congenital factor V deficiency

Computational evidence

Protein change
AlphaMissense	0.4763	ambiguous
REVEL	0.411	indeterminate
SaProt	LLR -7.52	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.1	GERP 2.1, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 45 kb · p 0.00099 · regional, not allelic
Overall
CADD	18.72	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 0.0747% African / African-American · 56/74,976 alleles

Filtering AF 0.059% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0534%

Overall 0.0049% 79/1,612,860 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0747%	1,339
Admixed American	0.03%	3,335
Remaining individualsnot grpmax-eligible	0.00801%	12,482

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.Val394Ala
Coding: c.1181T>C
MANE Select: NM_000130
dbSNP: rs142875000
Type: single nucleotide variant
Location: chr1:169552672 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.57 · 23 PDB
Residue 394: a β-strand; the f5/8 type a 2 domain; the plastocyanin-like 3 domain

Full F5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital factor V deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Congenital factor V deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 1 000 000 (Europe)

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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-val394ala (accessed [today's date]).

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