HHAT p.Pro319=
c.957C>T · rs142420396 · VCV729041
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.66%, eas)
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 -7.3 | GERP -4.2 |
| Overall | ||
| CADD | 1.024 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.66%
East Asian · 296/44,866 alleles
Filtering AF
0.598%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.574%
Overall
0.0522%
843/1,614,176 alleles · rare
exomes 745/1,461,852 · genomes 98/152,324 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.66% | 152 |
| Finnishnot grpmax-eligible | 0.201% | 496 |
| Admixed American | 0.0983% | 1,017 |
| Remaining individualsnot grpmax-eligible | 0.064% | 1,563 |
| European (non-Finnish) | 0.0242% | 4,140 |
| South Asian | 0.0231% | 4,337 |
| Middle Eastern | 0.0165% | 6,062 |
| African / African-American | 0.016% | 6,255 |
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.Pro319=
- Coding
- c.957C>T
- MANE Select
- NM_018194
- dbSNP
- rs142420396
- Type
- single nucleotide variant
- Location
- chr1:210464605 (GRCh38)
- Gene constraint
- LOEUF 0.785 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.07 · 10 PDB
- Residue 319
- 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.Ala389= Benign ★★ same type
- HHAT p.Arg176Cys 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-pro319 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown