HAP1 p.Thr434=
c.1302G>T · rs374580379 · VCV3043866
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00567%, nfe)
Conditions
1
HAP1-related disorder
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 0.037 | GERP -1.6, phastCons 0.36 |
| Overall | ||
| CADD | 1.545 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00567%
European (non-Finnish) · 66/1,164,002 alleles
Filtering AF
0.00457%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00417%
Overall
0.00452%
72/1,592,920 alleles · very rare
exomes 68/1,440,768 · genomes 4/152,152 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00567% | 17,636 |
| Remaining individualsnot grpmax-eligible | 0.00486% | 20,586 |
| African / African-American | 0.00268% | 37,332 |
| South Asian | 0.00111% | 89,928 |
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
- HAP1
- Protein
- p.Thr434=
- Coding
- c.1302G>T
- MANE Select
- NM_177977
- dbSNP
- rs374580379
- Type
- single nucleotide variant
- Location
- chr17:41727118 (GRCh38)
- Gene constraint
- LOEUF 1.31 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 64.28
- Residue 434
- the hap1 n-terminal domain
Disease context
HAP1-related disorder
Similar variants
- HAP1 c.1201-4C>T Likely benign same condition
- HAP1 c.1201-7C>T Likely benign same condition
- HAP1 c.470-7C>G Likely benign same condition
- HAP1 p.Ala21= Likely benign same condition
- HAP1 p.Ala505Val Benign same condition
- HAP1 p.Arg116Trp Likely benign same condition
- HAP1 p.Asp339Asn Likely benign same condition
- HAP1 p.Leu408Phe Benign ⚠ same condition
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/hap1-p-thr434 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown