Is F9 p.Val153Met (c.457G>A) pathogenic?

F9 p.Val153Met (c.457G>A) is classified Likely pathogenic in F9 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-12-06). AlphaMissense: likely benign (0.1402); Very rare (popmax 0.000112%, nfe); Associated with F9-related disorder.

What condition is associated with F9 p.Val153Met (c.457G>A)?

F9 p.Val153Met (c.457G>A) is associated with F9-related disorder (ClinVar).

How common is F9 p.Val153Met (c.457G>A) in the general population?

F9 p.Val153Met (c.457G>A) is very rare (popmax 0.000112%, nfe) (gnomAD).

What do computational predictors say about F9 p.Val153Met (c.457G>A)?

AlphaMissense predicts likely benign (score 0.1402) — an in-silico prediction, not a clinical call.

F9 p.Val153Met

c.457G>A · rs1927766998 · VCV2631132

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1402 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

F9-related disorder

Computational evidence

Protein change
AlphaMissense	0.1402	likely benign ⚠ discordant with ClinVar
REVEL	0.642	indeterminate
SaProt	LLR -8.77	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.5	GERP 3, phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 25 kb · p 2.3e-14 · regional, not allelic
Overall
CADD	20.9	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 0.000112% European (non-Finnish) · 1/894,492 alleles

Overall 9.12e-05% 1/1,096,972 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: F9
Protein: p.Val153Met
Coding: c.457G>A
MANE Select: NM_000133
dbSNP: rs1927766998
Type: single nucleotide variant
Location: chrX:139548428 (GRCh38)
Structure: AlphaFold pLDDT 80.45 · 57 PDB
Residue 153: a β-strand; the egf-like 2 domain; a disulfide bond

Full F9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

F9-related disorder

Similar variants

F9 p.Val153= Pathogenic/Likely pathogenic ★★ same residue
F9 p.Val153Ala Likely pathogenic ★ ⚠ same residue
F9 p.Arg226Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
F9 p.Arg379Gln Pathogenic ★★ ⚠ same condition
F9 p.Arg384Ter Pathogenic ★★ same condition
F9 p.Arg43Leu Pathogenic ★★ ⚠ same condition
F9 p.Cys28Arg Pathogenic/Likely pathogenic ★★ ⚠ same condition
F9 p.Gln241Arg 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/f9-p-val153met (accessed [today's date]).

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