Is F5 p.Pro313Ala (c.937C>G) pathogenic?

F5 p.Pro313Ala (c.937C>G) is classified Uncertain significance in F5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-29). AlphaMissense: likely benign (0.0958); Ultra-rare (popmax 0.0133%, amr); Associated with congenital factor V deficiency.

What condition is associated with F5 p.Pro313Ala (c.937C>G)?

F5 p.Pro313Ala (c.937C>G) is associated with congenital factor V deficiency (ClinVar).

How common is F5 p.Pro313Ala (c.937C>G) in the general population?

F5 p.Pro313Ala (c.937C>G) is ultra-rare (popmax 0.0133%, amr) (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.Pro313Ala (c.937C>G)?

AlphaMissense predicts likely benign (score 0.0958) — an in-silico prediction, not a clinical call.

F5 p.Pro313Ala

c.937C>G · VCV3710217

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0958 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

congenital factor V deficiency

Computational evidence

Protein change
AlphaMissense	0.0958	likely benign
REVEL	0.378	indeterminate
SaProt	LLR -5.99	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.24	donor gain · deltas
Constraint at this position
Conservation	phyloP 3.4	GERP 0.15, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 45 kb · p 0.00099 · regional, not allelic
Overall
CADD	17.15	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 0.0133% Admixed American · 8/59,980 alleles

Filtering AF 0.00662% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00483%

Overall 0.000867% 14/1,613,870 alleles · ultra-rare exomes 12/1,461,796 · genomes 2/152,074 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0133%	7,497
European (non-Finnish)	0.000508%	196,659

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.Pro313Ala
Coding: c.937C>G
MANE Select: NM_000130
Type: single nucleotide variant
Location: chr1:169556661 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.57 · 23 PDB
Residue 313: an α-helix; the f5/8 type a 1 domain; the plastocyanin-like 2 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-pro313ala (accessed [today's date]).

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