HTT p.Thr2725=
c.8175A>C · rs201467885 · VCV1599414
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.34%, nfe)
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 -8.6 | GERP -3.7 |
| Overall | ||
| CADD | 0.092 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.34%
European (non-Finnish) · 4,010/1,179,934 alleles
Filtering AF
0.331%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.327%
Overall
0.272%
4,389/1,614,138 alleles · rare
exomes 4,108/1,461,776 · genomes 281/152,362 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.34% | 294 |
| Admixed American | 0.292% | 343 |
| Remaining individualsnot grpmax-eligible | 0.221% | 453 |
| African / African-American | 0.0706% | 1,416 |
| Middle Eastern | 0.0495% | 2,021 |
| Finnishnot grpmax-eligible | 0.0141% | 7,117 |
| South Asian | 0.0011% | 91,090 |
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.Thr2725=
- Coding
- c.8175A>C
- MANE Select
- NM_001388492
- dbSNP
- rs201467885
- Type
- single nucleotide variant
- Location
- chr4:3229952 (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-thr2725 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown