HAL p.His531=
c.1593C>T · rs185963433 · VCV750733
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0217%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.295 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -5.4 | GERP -1.2 |
| Overall | ||
| CADD | 1.835 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0217%
Admixed American · 13/60,024 alleles
Filtering AF
0.0127%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0101%
Overall
0.00198%
32/1,612,884 alleles · ultra-rare
exomes 25/1,460,560 · genomes 7/152,324 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0217% | 4,617 |
| African / African-American | 0.00267% | 37,517 |
| European (non-Finnish) | 0.00144% | 69,342 |
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
- HAL
- Protein
- p.His531=
- Coding
- c.1593C>T
- MANE Select
- NM_002108
- dbSNP
- rs185963433
- Type
- single nucleotide variant
- Location
- chr12:95978005 (GRCh38)
- Gene constraint
- LOEUF 1.213 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.83
Similar variants
- HAL c.*392C>T Uncertain significance ★★ same type
- HAL p.Arg9Cys Uncertain significance ★★ ⚠ same type
- HAL p.Asn476Lys Uncertain significance ★★ ⚠ same type
- HAL p.Glu472Lys Uncertain significance ★★ ⚠ same type
- HAL p.Gly165Ser Uncertain significance ★★ ⚠ same type
- HAL p.Ile458Thr Uncertain significance ★★ ⚠ same type
- HAL p.Leu242Met Uncertain significance ★★ ⚠ same type
- HAL p.Phe485Leu 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/hal-p-his531 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown