Is F5 p.Leu744Phe (c.2232G>C) pathogenic?

F5 p.Leu744Phe (c.2232G>C) is classified Uncertain significance in F5 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-28). AlphaMissense: likely benign (0.1032); Absent from gnomAD v4.1; Associated with factor V deficiency.

What condition is associated with F5 p.Leu744Phe (c.2232G>C)?

F5 p.Leu744Phe (c.2232G>C) is associated with factor V deficiency (ClinVar).

How common is F5 p.Leu744Phe (c.2232G>C) in the general population?

F5 p.Leu744Phe (c.2232G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about F5 p.Leu744Phe (c.2232G>C)?

AlphaMissense predicts likely benign (score 0.1032) — an in-silico prediction, not a clinical call.

F5 p.Leu744Phe

c.2232G>C · rs2101820303 · VCV1098463

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1032 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

factor V deficiency

Computational evidence

Protein change
AlphaMissense	0.1032	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	LLR -7.29	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.25	GERP -1.3
Regional constraint	o/e 0.92	unconstrained · MANE · 45 kb · p 0.00099 · regional, not allelic
Overall
CADD	13.33	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: F5
Protein: p.Leu744Phe
Coding: c.2232G>C
MANE Select: NM_000130
dbSNP: rs2101820303
Type: single nucleotide variant
Location: chr1:169542858 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.57 · 23 PDB
Residue 744: the 'b' region

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

Disease context

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

Similar variants

F5 c.1297-2A>G Pathogenic/Likely pathogenic ★★ same condition
F5 p.Arg740Ter Pathogenic/Likely pathogenic ★★ same condition
F5 p.Tyr1730Cys Pathogenic/Likely pathogenic ★★ same condition
F5 c.-110C>A Uncertain significance ★★ same condition
F5 p.Arg1715Gln Uncertain significance ★★ ⚠ same condition
F5 p.Arg2055Gln Uncertain significance ★★ ⚠ same condition
F5 p.Arg376Ser Uncertain significance ★★ ⚠ same condition
F5 p.Glu1152Ala Uncertain significance ★★ ⚠ same condition

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-leu744phe (accessed [today's date]).

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