HMBS p.Asp240=
c.720T>C · rs770760881 · VCV1958910
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0178%, 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 -0.088 | GERP 0.006, phastCons 0.84 |
| Overall | ||
| CADD | 4.734 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0178%
East Asian · 8/44,902 alleles
Filtering AF
0.00883%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00641%
Overall
0.000558%
9/1,614,006 alleles · ultra-rare
exomes 8/1,461,870 · genomes 1/152,136 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0178% | 5,613 |
| South Asian | 0.0011% | 91,090 |
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
- HMBS
- Protein
- p.Asp240=
- Coding
- c.720T>C
- MANE Select
- NM_000190
- dbSNP
- rs770760881
- Type
- single nucleotide variant
- Location
- chr11:119092472 (GRCh38)
- Gene constraint
- LOEUF 0.546 · pLI 0.81 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 90.54 · 11 PDB
Similar variants
- HMBS p.Asp240Asn Uncertain significance ★★ ⚠ same residue
- HMBS p.Asp240Gly Pathogenic ★ same residue
- HMBS p.Asp240fs Pathogenic ★ same residue
- HMBS c.160+5G>C Pathogenic/Likely pathogenic ★★ same type
- HMBS c.345-1G>A Pathogenic ★★ same type
- HMBS c.613-1G>A Pathogenic ★★ same type
- HMBS c.826-2A>T Pathogenic/Likely pathogenic ★★ same type
- HMBS c.912+2T>C 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/hmbs-p-asp240 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown