Is F9 p.Met8Val (c.22A>G) pathogenic?

F9 p.Met8Val (c.22A>G) is classified Uncertain significance in F9 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-04-30). AlphaMissense: likely benign (0.1064); Very rare (popmax 0.000447%, nfe); Associated with F9-related disorder.

What condition is associated with F9 p.Met8Val (c.22A>G)?

F9 p.Met8Val (c.22A>G) is associated with F9-related disorder (ClinVar).

How common is F9 p.Met8Val (c.22A>G) in the general population?

F9 p.Met8Val (c.22A>G) is very rare (popmax 0.000447%, nfe) (gnomAD).

What do computational predictors say about F9 p.Met8Val (c.22A>G)?

AlphaMissense predicts likely benign (score 0.1064) — an in-silico prediction, not a clinical call.

F9 p.Met8Val

c.22A>G · VCV3354182

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1064 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000447%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

F9-related disorder

Computational evidence

Protein change
AlphaMissense	0.1064	likely benign
REVEL	0.525	indeterminate
SaProt	LLR -6.73	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 11	GERP 5.3, phastCons 1
Regional constraint	o/e 1.17	unconstrained · MANE · 6,280 bp · p 0.32 · regional, not allelic
Overall
CADD	20.3	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

Grpmax group 0.000447% European (non-Finnish) · 4/894,898 alleles

Filtering AF 0.000105% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.1e-05%

Overall 0.000365% 4/1,097,380 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.Met8Val
Coding: c.22A>G
MANE Select: NM_000133
Type: single nucleotide variant
Location: chrX:139530786 (GRCh38)
Structure: AlphaFold pLDDT 80.45 · 57 PDB

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

Disease context

F9-related disorder

Similar variants

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
F9 c.277+1G>T Pathogenic ★ same condition
F9 p.Cys155Ser 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-met8val (accessed [today's date]).

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