HMBS p.Ile110=
c.330C>T · rs143348479 · VCV716322
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.419%, 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 -1.3 | GERP -2.8, phastCons 0.001 |
| Overall | ||
| CADD | 8.392 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.419%
African / African-American · 314/75,018 alleles
Filtering AF
0.38%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.365%
Overall
0.0239%
386/1,612,424 alleles · rare
exomes 190/1,460,136 · genomes 196/152,288 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.419% | 239 |
| Admixed American | 0.0601% | 1,665 |
| Remaining individualsnot grpmax-eligible | 0.0368% | 2,716 |
| Middle Eastern | 0.0331% | 3,024 |
| South Asian | 0.0022% | 45,393 |
| European (non-Finnish) | 0.000763% | 130,985 |
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.Ile110=
- Coding
- c.330C>T
- MANE Select
- NM_000190
- dbSNP
- rs143348479
- Type
- single nucleotide variant
- Location
- chr11:119089746 (GRCh38)
- Gene constraint
- LOEUF 0.546 · pLI 0.81 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 90.54 · 11 PDB
- Residue 110
- a β-strand
Similar variants
- HMBS p.Ile110Val Uncertain significance ★ ⚠ 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
- HMBS c.913-1G>A Pathogenic ★★ same type
- HMBS c.913-1G>C 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/hmbs-p-ile110 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown