IMPG2 p.Val277Phe
c.829G>T · VCV4963561
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.3866 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
0/2 damaging
REVEL, SaProt · AlphaMissense indeterminate
Computational evidence
| Protein change | ||
| AlphaMissense | 0.3866 | ambiguous |
|---|---|---|
| REVEL | 0.274 | benign-leaning |
| SaProt | LLR -7.63 | tolerated |
| ⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate. | ||
| Splicing | ||
| SpliceAI | Δ0.67 | acceptor loss · deltas |
| Pangolin | Δ0.46 | loss · gain 0.01 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 3.2 | GERP 1, phastCons 1 |
| Regional constraint | o/e 0.98 | unconstrained · MANE · 93 kb · p 0.41 · regional, not allelic |
| Overall | ||
| CADD | 23.9 | 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
- IMPG2
- Protein
- p.Val277Phe
- Coding
- c.829G>T
- MANE Select
- NM_016247
- Type
- single nucleotide variant
- Location
- chr3:101269573 (GRCh38)
- Gene constraint
- LOEUF 0.773 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 54.28
- Residue 277
- a UniProt-annotated variant site (in rp56); a UniProt-annotated variant site (in vmd5); the sea 1 domain
Similar variants
- IMPG2 p.Val277Ile Uncertain significance ★ ⚠ same residue
- IMPG2 p.Val277= Likely benign ★ same residue
- IMPG2 c.1240-1G>A Likely pathogenic ★★ same type
- IMPG2 c.1240-2A>G Pathogenic/Likely pathogenic ★★ same type
- IMPG2 c.502-2A>G Likely pathogenic ★★ same type
- IMPG2 c.583+1G>C Pathogenic/Likely pathogenic ★★ same type
- IMPG2 c.667-1G>A Pathogenic/Likely pathogenic ★★ same type
- IMPG2 c.828+1G>A Pathogenic/Likely pathogenic ★★ 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/impg2-p-val277phe (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown