Is F5 p.Val238Glu (c.713T>A) pathogenic?

F5 p.Val238Glu (c.713T>A) is classified Uncertain significance in F5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-07). AlphaMissense: likely benign (0.2326); Very rare (popmax 6.84e-05%); Associated with congenital factor V deficiency.

What condition is associated with F5 p.Val238Glu (c.713T>A)?

F5 p.Val238Glu (c.713T>A) is associated with congenital factor V deficiency (ClinVar).

How common is F5 p.Val238Glu (c.713T>A) in the general population?

F5 p.Val238Glu (c.713T>A) is very rare (popmax 6.84e-05%) (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.Val238Glu (c.713T>A)?

AlphaMissense predicts likely benign (score 0.2326) — an in-silico prediction, not a clinical call.

F5 p.Val238Glu

c.713T>A · rs1428045772 · VCV3013768

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2326 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital factor V deficiency

Computational evidence

Protein change
AlphaMissense	0.2326	likely benign
REVEL	0.693	pathogenic-leaning
SaProt	LLR -12.55	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.4	GERP 1.1, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 45 kb · p 0.00099 · regional, not allelic
Overall
CADD	20.2	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 6.84e-05%

Overall 6.84e-05% 1/1,461,538 alleles · very rare

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.Val238Glu
Coding: c.713T>A
MANE Select: NM_000130
dbSNP: rs1428045772
Type: single nucleotide variant
Location: chr1:169559170 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.57 · 23 PDB
Residue 238: a β-strand; 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)

Similar variants

F5 p.Val238= Likely benign ★ same residue
F5 c.1297-2A>G Pathogenic/Likely pathogenic ★★ same condition
F5 p.Arg1030Ter Pathogenic ★★ same condition
F5 p.Arg146Ter Pathogenic/Likely pathogenic ★★ same condition
F5 p.Arg1621Ter Pathogenic/Likely pathogenic ★★ same condition
F5 p.Arg1634Ter Pathogenic/Likely pathogenic ★★ same condition
F5 p.Arg2102His Pathogenic/Likely pathogenic ★★ same condition
F5 p.Arg740Ter Pathogenic/Likely pathogenic ★★ 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-val238glu (accessed [today's date]).

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