ASAH1 p.Leu73=
c.219A>G · rs141785977 · VCV917670
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0322%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.36 | GERP 1.7, phastCons 0.25 |
| Overall | ||
| CADD | 8.521 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0322%
African / African-American · 24/74,510 alleles
Filtering AF
0.0221%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0188%
Overall
0.00172%
27/1,573,296 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0322% | 3,105 |
| Admixed American | 0.00334% | 29,927 |
| East Asian | 0.00224% | 44,682 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- ASAH1
- Protein
- p.Leu73=
- Coding
- c.219A>G
- MANE Select
- NM_177924
- dbSNP
- rs141785977
- Type
- single nucleotide variant
- Location
- chr8:18069876 (GRCh38)
- Gene constraint
- LOEUF 1.435 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.97 · 2 PDB
- Residue 73
- a disulfide bond; an α-helix
Similar variants
- ASAH1 c.1098+1G>T Pathogenic/Likely pathogenic ★★ same type
- ASAH1 c.125+1G>A Pathogenic ★★ same type
- ASAH1 c.457+4A>G Pathogenic/Likely pathogenic ★★ same type
- ASAH1 c.648+1G>C Likely pathogenic ★★ same type
- ASAH1 c.786-2A>G Likely pathogenic ★★ same type
- ASAH1 p.Arg254Gly Pathogenic ★★ same type
- ASAH1 p.Arg296Ter Pathogenic ★★ same type
- ASAH1 p.Arg333Cys 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/asah1-p-leu73 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown