Is F7 p.Asp381Tyr (c.1141G>T) pathogenic?

F7 p.Asp381Tyr (c.1141G>T) is classified Uncertain significance in F7 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-01-19). AlphaMissense: likely pathogenic (0.9551); Absent from gnomAD v4.1; Associated with F7-related disorder.

What condition is associated with F7 p.Asp381Tyr (c.1141G>T)?

F7 p.Asp381Tyr (c.1141G>T) is associated with F7-related disorder (ClinVar).

How common is F7 p.Asp381Tyr (c.1141G>T) in the general population?

F7 p.Asp381Tyr (c.1141G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about F7 p.Asp381Tyr (c.1141G>T)?

AlphaMissense predicts likely pathogenic (score 0.9551) — an in-silico prediction, not a clinical call.

F7 p.Asp381Tyr

c.1141G>T · rs773186886 · VCV3034368

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9551 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

F7-related disorder

Computational evidence

Protein change
AlphaMissense	0.9551	likely pathogenic · top 7% in F7
REVEL	0.958	strongly pathogenic-leaning
SaProt	LLR -12.31	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 13 kb · p 0.22 · regional, not allelic
Overall
CADD	29.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM D403Y vs ClinVar D381Y) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: F7
Protein: p.Asp381Tyr
Coding: c.1141G>T
MANE Select: NM_019616
dbSNP: rs773186886
Type: single nucleotide variant
Location: chr13:113118814 (GRCh38)
Gene constraint: LOEUF 1.113 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 82.64 · 114 PDB
Residue 381: a turn; a disulfide bond; the peptidase s1 domain

Full F7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

F7-related disorder

Similar variants

F7 p.Ala332Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
F7 p.Thr397Met Pathogenic ★★ ⚠ same condition
F7 c.-32A>C Likely pathogenic ★ same condition
F7 p.Trp239Ter Likely pathogenic ★ same condition
F7 p.Asp280Asn Conflicting classifications of pathogenicity ★ ⚠ same condition
F7 p.Cys173Tyr Uncertain significance ★ ⚠ same condition
F7 p.Val206Leu Uncertain significance ★ ⚠ same condition
F7 p.Arg342Gly 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/f7-p-asp381tyr (accessed [today's date]).

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