Is F10 p.Val424Leu (c.1270G>C) pathogenic?

F10 p.Val424Leu (c.1270G>C) is classified Uncertain significance in F10 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-17). AlphaMissense: likely pathogenic (0.6615); Very rare (popmax 0.00446%, eas); Associated with Inborn genetic diseases.

What condition is associated with F10 p.Val424Leu (c.1270G>C)?

F10 p.Val424Leu (c.1270G>C) is associated with Inborn genetic diseases (ClinVar).

How common is F10 p.Val424Leu (c.1270G>C) in the general population?

F10 p.Val424Leu (c.1270G>C) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about F10 p.Val424Leu (c.1270G>C)?

AlphaMissense predicts likely pathogenic (score 0.6615) — an in-silico prediction, not a clinical call.

F10 p.Val424Leu

c.1270G>C · rs201301913 · VCV2547739

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6615 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6615	likely pathogenic
REVEL	0.695	pathogenic-leaning
SaProt	LLR -9.75	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.9, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 10 kb · p 2.9e-09 · regional, not allelic
Overall
CADD	25.4	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 0.00446% East Asian · 2/44,882 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000137% 2/1,460,922 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: F10
Protein: p.Val424Leu
Coding: c.1270G>C
MANE Select: NM_000504
dbSNP: rs201301913
Type: single nucleotide variant
Location: chr13:113149320 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.47 · 192 PDB
Residue 424: the peptidase s1 domain; a β-strand; a disulfide bond

Full F10 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

F10 p.Glu268Lys Uncertain significance ★★ ⚠ same condition
F10 p.Ala185Asp Uncertain significance ★ ⚠ same condition
F10 p.Ala250Val Uncertain significance ★ same condition
F10 p.Ala457Thr Uncertain significance ★ ⚠ same condition
F10 p.Arg180Gly Uncertain significance ★ ⚠ same condition
F10 p.Arg28Thr Uncertain significance ★ ⚠ same condition
F10 p.Asn97Lys Uncertain significance ★ same condition
F10 p.Asp159Asn 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/f10-p-val424leu (accessed [today's date]).

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