Is F7 p.Val227Asp (c.680T>A) pathogenic?

F7 p.Val227Asp (c.680T>A) is classified Uncertain significance in F7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-11). AlphaMissense: likely pathogenic (0.9697); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with F7 p.Val227Asp (c.680T>A)?

F7 p.Val227Asp (c.680T>A) is associated with Inborn genetic diseases (ClinVar).

How common is F7 p.Val227Asp (c.680T>A) in the general population?

F7 p.Val227Asp (c.680T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about F7 p.Val227Asp (c.680T>A)?

AlphaMissense predicts likely pathogenic (score 0.9697) — an in-silico prediction, not a clinical call.

F7 p.Val227Asp

c.680T>A · VCV4619063

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9697 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9697	likely pathogenic · top 5% in F7
REVEL	0.792	moderately pathogenic-leaning
SaProt	LLR -15.62	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 4.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 13 kb · p 0.22 · regional, not allelic
Overall
CADD	23.9	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 V249D vs ClinVar V227D) — 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.Val227Asp
Coding: c.680T>A
MANE Select: NM_019616
Type: single nucleotide variant
Location: chr13:113117537 (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 227: a β-strand; a disulfide bond; the peptidase s1 domain

Full F7 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

F7 p.Arg434His Uncertain significance ★★ ⚠ same condition
F7 p.Asp234Asn Uncertain significance ★★ ⚠ same condition
F7 p.Cys232Ser Uncertain significance ★★ ⚠ same condition
F7 p.Glu27Lys Uncertain significance ★★ ⚠ same condition
F7 p.His30Tyr Uncertain significance ★★ ⚠ same condition
F7 p.Lys147Arg Uncertain significance ★★ ⚠ same condition
F7 p.Thr345Ser Uncertain significance ★★ ⚠ same condition
F7 p.Trp225Cys 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/f7-p-val227asp (accessed [today's date]).

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