Is F5 p.Asp96His (c.286G>C) pathogenic?

F5 p.Asp96His (c.286G>C) is classified Pathogenic in F5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-08). AlphaMissense: likely pathogenic (0.9057); Ultra-rare (popmax 0.0491%, eas); Associated with congenital factor V deficiency.

What condition is associated with F5 p.Asp96His (c.286G>C)?

F5 p.Asp96His (c.286G>C) is associated with congenital factor V deficiency (ClinVar).

How common is F5 p.Asp96His (c.286G>C) in the general population?

F5 p.Asp96His (c.286G>C) is ultra-rare (popmax 0.0491%, eas) (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.Asp96His (c.286G>C)?

AlphaMissense predicts likely pathogenic (score 0.9057) — an in-silico prediction, not a clinical call.

F5 p.Asp96His

c.286G>C · rs747215273 · VCV2734026

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9057 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0491%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital factor V deficiency

Computational evidence

Protein change
AlphaMissense	0.9057	likely pathogenic ✓ concordant with ClinVar · top 6% in F5
REVEL	0.981	strongly pathogenic-leaning
SaProt	LLR -12.15	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 45 kb · p 0.00099 · regional, not allelic
Overall
CADD	27.6	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 0.0491% East Asian · 22/44,838 alleles

Filtering AF 0.0332% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.028%

Overall 0.00143% 23/1,613,106 alleles · ultra-rare exomes 20/1,461,018 · genomes 3/152,088 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0491%	2,038
Remaining individualsnot grpmax-eligible	0.0016%	62,424

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.Asp96His
Coding: c.286G>C
MANE Select: NM_000130
dbSNP: rs747215273
Type: single nucleotide variant
Location: chr1:169572308 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.57 · 23 PDB
Residue 96: the f5/8 type a 1 domain; the plastocyanin-like 1 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.Asp96= 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-asp96his (accessed [today's date]).

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