Is F5 p.Val36Met (c.106G>A) pathogenic?

F5 p.Val36Met (c.106G>A) is classified Conflicting classifications of pathogenicity in F5 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-11-18). AlphaMissense: ambiguous (0.5357); Rare (popmax 0.484%, afr); Associated with Inborn genetic diseases.

What condition is associated with F5 p.Val36Met (c.106G>A)?

F5 p.Val36Met (c.106G>A) is associated with Inborn genetic diseases, congenital factor V deficiency (ClinVar).

How common is F5 p.Val36Met (c.106G>A) in the general population?

F5 p.Val36Met (c.106G>A) is rare (popmax 0.484%, afr) (gnomAD).

What do computational predictors say about F5 p.Val36Met (c.106G>A)?

AlphaMissense predicts ambiguous (score 0.5357) — an in-silico prediction, not a clinical call.

F5 p.Val36Met

c.106G>A · rs147487854 · VCV710594

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5357 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.484%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5357	ambiguous
REVEL	0.668	pathogenic-leaning
SaProt	LLR -9.79	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.77	GERP 0.99, phastCons 0.43
Regional constraint	o/e 0.92	unconstrained · MANE · 45 kb · p 0.00099 · regional, not allelic
Overall
CADD	22.2	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 0.484% African / African-American · 363/75,066 alleles

Filtering AF 0.443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.426%

Overall 0.0256% 413/1,614,202 alleles · rare exomes 203/1,461,866 · genomes 210/152,336 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.484%	207
Admixed American	0.035%	2,859
Remaining individualsnot grpmax-eligible	0.0272%	3,677
European (non-Finnish)	0.00102%	98,336

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.Val36Met
Coding: c.106G>A
MANE Select: NM_000130
dbSNP: rs147487854
Type: single nucleotide variant
Location: chr1:169586281 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.57 · 23 PDB
Residue 36: a β-strand; 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: congenital factor V deficiency

Similar variants

F5 p.Val36= 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-val36met (accessed [today's date]).

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