HTT p.Val977=
c.2931C>A · rs767738365 · VCV2654596
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.095%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.40 | donor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.1 | GERP 0.83, phastCons 1 |
| Overall | ||
| CADD | 15.79 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.095%
Admixed American · 57/59,998 alleles
Filtering AF
0.0752%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0681%
Overall
0.0157%
254/1,613,964 alleles · ultra-rare
exomes 216/1,461,734 · genomes 38/152,230 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.095% | 1,053 |
| Middle Eastern | 0.0493% | 2,027 |
| European (non-Finnish) | 0.0155% | 6,448 |
| Remaining individualsnot grpmax-eligible | 0.0128% | 7,810 |
| African / African-American | 0.004% | 24,977 |
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.Val977=
- Coding
- c.2931C>A
- MANE Select
- NM_001388492
- dbSNP
- rs767738365
- Type
- single nucleotide variant
- Location
- chr4:3140642 (GRCh38)
- Structure
- AlphaFold pLDDT 85.38 · 30 PDB
Similar variants
- HTT p.Val977Ile Uncertain significance ★ ⚠ same residue
- 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
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-val977 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown