HHAT p.Ala389=
c.1167A>G · rs35867665 · VCV787222
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.44%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.51 | GERP -4.8 |
| Overall | ||
| CADD | 2.951 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.44%
African / African-American · 2,585/75,050 alleles
Filtering AF
3.33%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.29%
Overall
0.272%
4,389/1,614,044 alleles · low-frequency
exomes 2,735/1,461,742 · genomes 1,654/152,302 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.44% | 29 |
| Middle Eastern | 0.858% | 117 |
| Admixed American | 0.581% | 172 |
| Remaining individualsnot grpmax-eligible | 0.437% | 229 |
| Ashkenazi Jewishnot grpmax-eligible | 0.233% | 429 |
| European (non-Finnish) | 0.0889% | 1,125 |
| South Asian | 0.0132% | 7,589 |
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
- HHAT
- Protein
- p.Ala389=
- Coding
- c.1167A>G
- MANE Select
- NM_018194
- dbSNP
- rs35867665
- Type
- single nucleotide variant
- Location
- chr1:210588021 (GRCh38)
- Gene constraint
- LOEUF 0.785 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.07 · 10 PDB
- Residue 389
- an α-helix; a UniProt-annotated variant site (in nnms; uncertain significance)
Similar variants
- HHAT p.Ala308Thr Uncertain significance ★★ ⚠ same type
- HHAT p.Arg176His Uncertain significance ★★ ⚠ same type
- HHAT p.Arg403Trp Uncertain significance ★★ ⚠ same type
- HHAT p.His379Tyr Uncertain significance ★★ ⚠ same type
- HHAT c.1245+19G>C Benign ★★ same type
- HHAT c.159+15C>A Benign ★★ same type
- HHAT p.Arg176Cys Benign ★★ ⚠ same type
- HHAT p.Arg312His Benign ★★ 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/hhat-p-ala389 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown