ALPP p.Ile337Met
c.1011C>G · VCV4640129
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.3632 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
2/2 damaging
REVEL, SaProt · AlphaMissense no call
Computational evidence
| Protein change | ||
| AlphaMissense | 0.3632 | ambiguous |
|---|---|---|
| REVEL | 0.727 | pathogenic-leaning |
| SaProt | LLR -13.19 | damaging |
| ⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>T here scores Δ0.25 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP -10 | |
| Regional constraint | o/e 0.01 | constrained · MANE · 594 bp · p 1.9e-31 · regional, not allelic |
| Overall | ||
| CADD | 14.55 | 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
- ALPP
- Protein
- p.Ile337Met
- Coding
- c.1011C>G
- MANE Select
- NM_001632
- Type
- single nucleotide variant
- Location
- chr2:232380850 (GRCh38)
- Gene constraint
- LOEUF 1.117 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.73 · 8 PDB
- Residue 337
- an α-helix
Similar variants
- ALPP c.865+8C>T Likely benign ★★ same type
- ALPP p.Ala176= Benign ★★ same type
- ALPP p.Arg231Pro Benign ★★ same type
- ALPP p.Arg36= Benign ★★ same type
- ALPP p.Glu37Gln Benign ★★ same type
- ALPP p.Gly233= Likely benign ★★ same type
- ALPP p.Gly63= Likely benign ★★ same type
- ALPP p.Phe331= Benign ★★ 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/alpp-p-ile337met (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown