HTT p.Asp2985=
c.8955C>T · rs374515950 · VCV1587766
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0517%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>G here scores Δ0.24 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -15 | GERP -3.3 |
| Overall | ||
| CADD | 0.024 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0517%
Admixed American · 31/59,946 alleles
Filtering AF
0.0374%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0325%
Overall
0.0201%
325/1,613,300 alleles · ultra-rare
exomes 288/1,461,006 · genomes 37/152,294 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0517% | 1,934 |
| Remaining individualsnot grpmax-eligible | 0.0432% | 2,314 |
| South Asian | 0.0253% | 3,949 |
| European (non-Finnish) | 0.0198% | 5,041 |
| African / African-American | 0.0107% | 9,378 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,594 |
| East Asian | 0.00223% | 44,868 |
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.Asp2985=
- Coding
- c.8955C>T
- MANE Select
- NM_001388492
- dbSNP
- rs374515950
- Type
- single nucleotide variant
- Location
- chr4:3238510 (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-asp2985 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown