FIG4 p.Val487Ala
c.1460T>C · VCV3278874
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.9979 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
1/2 damaging
AlphaMissense, SaProt · REVEL indeterminate
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9979 | likely pathogenic · top 7% in FIG4 |
|---|---|---|
| REVEL | 0.451 | indeterminate |
| SaProt | LLR -8.60 | tolerated |
| ⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 5 | GERP 2, phastCons 1 |
| Regional constraint | o/e 0.69 | unconstrained · MANE · 34 kb · p 8.8e-09 · regional, not allelic |
| Overall | ||
| CADD | 27.0 | 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
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
- FIG4
- Protein
- p.Val487Ala
- Coding
- c.1460T>C
- MANE Select
- NM_014845
- Type
- single nucleotide variant
- Location
- chr6:109765038 (GRCh38)
- Gene constraint
- LOEUF 0.966 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.65 · 1 PDB
- Residue 487
- the sac domain
Similar variants
- FIG4 c.2459+1G>A Pathogenic ★★ same condition
- FIG4 p.Arg381Ter Pathogenic ★★ same condition
- FIG4 p.Gln198Ter Pathogenic/Likely pathogenic ★★ same condition
- FIG4 p.Leu643Ter Pathogenic ★★ same condition
- FIG4 p.Trp246Ter Pathogenic ★★ same condition
- FIG4 p.Tyr177Ter Pathogenic ★★ same condition
- FIG4 c.2376+4C>T Uncertain significance ★★ same condition
- FIG4 p.Ala308Val 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/fig4-p-val487ala (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown