Is FGF8 p.Val96Asp (c.287T>A) pathogenic?

FGF8 p.Val96Asp (c.287T>A) is classified Likely pathogenic in FGF8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-01). AlphaMissense: likely pathogenic (0.9988); Absent from gnomAD v4.1.

How common is FGF8 p.Val96Asp (c.287T>A) in the general population?

FGF8 p.Val96Asp (c.287T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FGF8 p.Val96Asp (c.287T>A)?

AlphaMissense predicts likely pathogenic (score 0.9988) — an in-silico prediction, not a clinical call.

FGF8 p.Val96Asp

c.287T>A · rs1057524676 · VCV392880

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9988 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9988	likely pathogenic ✓ concordant with ClinVar · top 7% in FGF8
REVEL	0.912	moderately pathogenic-leaning
SaProt	LLR -14.89	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 11	GERP 2.3, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 5,291 bp · p 0.0067 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V85D vs ClinVar V96D) — 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: FGF8
Protein: p.Val96Asp
Coding: c.287T>A
MANE Select: NM_033163
dbSNP: rs1057524676
Type: single nucleotide variant
Location: chr10:101774782 (GRCh38)
Gene constraint: LOEUF 0.765 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 81.34 · 1 PDB
Residue 85 UniProt numbering: a β-strand

Full FGF8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FGF8 c.157-1G>A Likely pathogenic ★★ same type
FGF8 p.Arg129Ter Pathogenic/Likely pathogenic ★★ same type
FGF8 p.Arg206Gln Likely pathogenic ★★ same type
FGF8 p.Thr119Met Likely pathogenic ★★ same type
FGF8 c.157-11A>G Uncertain significance ★★ same type
FGF8 p.Ala147Thr Uncertain significance ★★ ⚠ same type
FGF8 p.Ala31Glu Uncertain significance ★★ ⚠ same type
FGF8 p.Arg195Trp Uncertain significance ★★ ⚠ same type

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/fgf8-p-val96asp (accessed [today's date]).

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