ASL p.Met230Leu
c.688A>T · VCV3911948
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely benign
0.2137 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
1/3 damaging
AlphaMissense, REVEL, SaProt
Computational evidence
| Protein change | ||
| AlphaMissense | 0.2137 | likely benign |
|---|---|---|
| REVEL | 0.688 | pathogenic-leaning |
| SaProt | LLR -6.81 | tolerated |
| ⇒ REVEL calls this damaging; AlphaMissense and SaProt do not. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 1.7, phastCons 1 |
| Regional constraint | o/e 0.87 | unconstrained · MANE · 17 kb · p 0.00078 · regional, not allelic |
| Overall | ||
| CADD | 20.5 | 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
- ASL
- Protein
- p.Met230Leu
- Coding
- c.688A>T
- MANE Select
- NM_000048
- Type
- single nucleotide variant
- Location
- chr7:66087761 (GRCh38)
- Gene constraint
- LOEUF 0.937 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 96.51 · 2 PDB
- Residue 230
- an α-helix
Similar variants
- ASL p.Met230Val Pathogenic/Likely pathogenic ★★ ⚠ same residue
- ASL p.Met230Ile Likely pathogenic ★ same residue
- ASL p.Met230Thr Likely pathogenic ★ same residue
- ASL c.1062+5G>C Likely pathogenic ★★ same type
- ASL c.1143+1G>T Pathogenic/Likely pathogenic ★★ same type
- ASL c.13-1G>C Pathogenic/Likely pathogenic ★★ same type
- ASL c.291+1G>T Likely pathogenic ★★ same type
- ASL c.348+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/asl-p-met230leu (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown