ASPH p.His530=
c.1590C>T · rs375608999 · VCV2073181
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0401%, eas)
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 3.9 | GERP 1.1, phastCons 1 |
| Overall | ||
| CADD | 8.683 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0401%
East Asian · 18/44,834 alleles
Filtering AF
0.0259%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0214%
Overall
0.00508%
82/1,613,550 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0401% | 2,491 |
| Remaining individualsnot grpmax-eligible | 0.0368% | 2,716 |
| South Asian | 0.0242% | 4,139 |
| European (non-Finnish) | 0.00153% | 65,539 |
| African / African-American | 0.00133% | 74,956 |
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
- ASPH
- Protein
- p.His530=
- Coding
- c.1590C>T
- MANE Select
- NM_004318
- dbSNP
- rs375608999
- Type
- single nucleotide variant
- Location
- chr8:61553067 (GRCh38)
- Gene constraint
- LOEUF 1.011 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 72.34 · 43 PDB
- Residue 530
- an α-helix
Similar variants
- ASPH p.Arg735Trp Likely pathogenic ★★ same type
- ASPH p.Tyr565Ter Pathogenic/Likely pathogenic ★★ same type
- ASPH p.Arg425Cys Uncertain significance ★★ ⚠ same type
- ASPH p.Arg753His Uncertain significance ★★ ⚠ same type
- ASPH p.Glu506Val Uncertain significance ★★ ⚠ same type
- ASPH p.Leu433Arg Uncertain significance ★★ ⚠ same type
- ASPH p.Ser299Asn Uncertain significance ★★ ⚠ same type
- ASPH p.Val214Met Uncertain significance ★★ ⚠ 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/asph-p-his530 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown