HTT p.Ala2751=
c.8253C>T · rs2229985 · VCV1600993
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.05%, afr)
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 -14 | GERP -3.4 |
| Overall | ||
| CADD | 0.777 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.05%
African / African-American · 790/75,054 alleles
Filtering AF
0.992%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.967%
Overall
0.0678%
1,095/1,613,936 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.05% | 95 |
| South Asian | 0.146% | 685 |
| Remaining individualsnot grpmax-eligible | 0.0864% | 1,157 |
| Admixed American | 0.07% | 1,429 |
| Middle Eastern | 0.033% | 3,031 |
| East Asian | 0.00891% | 11,220 |
| European (non-Finnish) | 0.00593% | 16,855 |
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.Ala2751=
- Coding
- c.8253C>T
- MANE Select
- NM_001045 · reported on NM_001388492
- dbSNP
- rs2229985
- Type
- single nucleotide variant
- Location
- chr4:3230030 (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-ala2751 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown