HHAT p.Thr368=
c.1104G>A · rs766659481 · VCV1518849
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00333%, amr)
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 -11 | GERP -4.8 |
| Overall | ||
| CADD | 0.674 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00333%
Admixed American · 2/60,002 alleles
Filtering AF
0.000553%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000211%
Overall
0.000867%
14/1,614,010 alleles · very rare
exomes 13/1,461,838 · genomes 1/152,172 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00333% | 30,001 |
| East Asian | 0.00223% | 44,876 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,482 |
| African / African-American | 0.00133% | 74,922 |
| South Asian | 0.0011% | 91,080 |
| European (non-Finnish) | 0.000678% | 147,503 |
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.Thr368=
- Coding
- c.1104G>A
- MANE Select
- NM_018194
- dbSNP
- rs766659481
- Type
- single nucleotide variant
- Location
- chr1:210587958 (GRCh38)
- Gene constraint
- LOEUF 0.785 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.07 · 10 PDB
- Residue 368
- an α-helix; a UniProt-annotated variant site (in nnms; uncertain significance)
Similar variants
- HHAT p.Thr368Met Uncertain significance ★ ⚠ same residue
- 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.Ala389= 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-thr368 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown