HTT p.Ala2304=
c.6912C>T · rs573397591 · VCV1538647
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.395%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 3.4 | GERP 2.1, phastCons 1 |
| Overall | ||
| CADD | 13.54 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.395%
South Asian · 349/88,466 alleles
Filtering AF
0.36%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.347%
Overall
0.0274%
437/1,593,544 alleles · rare
exomes 413/1,441,200 · genomes 24/152,344 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.395% | 253 |
| Middle Eastern | 0.1% | 1,000 |
| Remaining individualsnot grpmax-eligible | 0.0309% | 3,238 |
| European (non-Finnish) | 0.00531% | 18,835 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00343% | 29,150 |
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
- HTT
- Protein
- p.Ala2304=
- Coding
- c.6912C>T
- MANE Select
- NM_001388492
- dbSNP
- rs573397591
- Type
- single nucleotide variant
- Location
- chr4:3214095 (GRCh38)
- Structure
- AlphaFold pLDDT 85.38 · 30 PDB
Similar variants
- HTT c.889+6G>T Uncertain significance ★★ same type
- HTT p.Ala2739Thr Uncertain significance ★★ same type
- HTT p.Arg1654Trp Uncertain significance ★★ same type
- HTT p.Arg1945Trp Uncertain significance ★★ same type
- HTT p.Asp1157Gly Uncertain significance ★★ same type
- HTT p.Asp920Asn Uncertain significance ★★ same type
- HTT p.Glu449Ala Uncertain significance ★★ ⚠ same type
- HTT p.Gly2084Arg 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/htt-p-ala2304 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown