Is F8 p.Val343Phe (c.1027G>T) pathogenic?

F8 p.Val343Phe (c.1027G>T) is classified Uncertain significance in F8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-29). AlphaMissense: likely benign (0.312); Very rare (popmax 0.00435%, amr); Associated with Inborn genetic diseases.

What condition is associated with F8 p.Val343Phe (c.1027G>T)?

F8 p.Val343Phe (c.1027G>T) is associated with Inborn genetic diseases (ClinVar).

How common is F8 p.Val343Phe (c.1027G>T) in the general population?

F8 p.Val343Phe (c.1027G>T) is very rare (popmax 0.00435%, amr) (gnomAD).

What do computational predictors say about F8 p.Val343Phe (c.1027G>T)?

AlphaMissense predicts likely benign (score 0.312) — an in-silico prediction, not a clinical call.

F8 p.Val343Phe

c.1027G>T · VCV4252404

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.312 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00435%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.312	likely benign
REVEL	0.646	pathogenic-leaning
SaProt	LLR -3.77	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.58	GERP -2.1, phastCons 0.34
Regional constraint	o/e 0.74	unconstrained · MANE · 38 kb · p 2.6e-06 · regional, not allelic
Overall
CADD	16.96	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 0.00435% Admixed American · 2/46,019 alleles

Filtering AF 0.00072% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00027%

Overall 0.00033% 4/1,211,429 alleles · very rare exomes 4/1,097,779 · genomes 0/113,650 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00435%	23,010
European (non-Finnish)	0.000223%	447,722

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: F8
Protein: p.Val343Phe
Coding: c.1027G>T
MANE Select: NM_000132
Type: single nucleotide variant
Location: chrX:154966670 (GRCh38)
Structure: AlphaFold pLDDT 61.20 · 29 PDB
Residue 343: a β-strand; the f5/8 type a 1 domain; the plastocyanin-like 2 domain

Full F8 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

Similar variants

F8 p.Tyr1699Phe Pathogenic ★★ ⚠ same condition
F8 p.Ala2108Val Uncertain significance ★★ ⚠ same condition
F8 p.Gln1049Lys Uncertain significance ★★ ⚠ same condition
F8 p.Gln1209Arg Uncertain significance ★★ ⚠ same condition
F8 p.Gly1729Trp Uncertain significance ★★ ⚠ same condition
F8 p.Leu13Phe Uncertain significance ★★ ⚠ same condition
F8 p.Ser1968Asn Uncertain significance ★★ ⚠ same condition
F8 p.Thr1670Ile Uncertain significance ★★ ⚠ 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/f8-p-val343phe (accessed [today's date]).

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