ASH1L p.Pro558=
c.1674A>G · VCV4914328
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000509%, nfe)
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 -1.8 | GERP 2 |
| Overall | ||
| CADD | 5.796 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000509%
European (non-Finnish) · 6/1,179,896 alleles
Filtering AF
0.000183%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00012%
Overall
0.000372%
6/1,613,938 alleles · very rare
exomes 6/1,461,704 · genomes 0/152,234 · joint denominator
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
- ASH1L
- Protein
- p.Pro558=
- Coding
- c.1674A>G
- MANE Select
- NM_018489
- Type
- single nucleotide variant
- Location
- chr1:155481196 (GRCh38)
- Gene constraint
- LOEUF 0.104 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Residue 558
- the 'disordered' region
Similar variants
- ASH1L p.Pro558Leu Uncertain significance ★ same residue
- ASH1L c.6178-2A>G Pathogenic ★★ same type
- ASH1L p.Arg1280Ter Pathogenic/Likely pathogenic ★★ same type
- ASH1L p.Arg1342Ter Pathogenic ★★ same type
- ASH1L p.Arg1527Ter Pathogenic ★★ same type
- ASH1L p.Arg1757Ter Likely pathogenic ★★ same type
- ASH1L p.Arg2535Ter Pathogenic ★★ same type
- ASH1L p.Arg2834Ter 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/ash1l-p-pro558 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown