HTT p.Ser2650=
c.7950G>A · VCV4966195
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0166%, mid)
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 -6.9 | GERP -3.8 |
| Overall | ||
| CADD | 0.148 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0166%
Middle Eastern · 1/6,018 alleles
Filtering AF
0.00368%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0033%
Overall
0.00405%
65/1,605,244 alleles · ultra-rare
exomes 58/1,453,018 · genomes 7/152,226 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0166% | 6,018 |
| Remaining individualsnot grpmax-eligible | 0.00967% | 10,341 |
| European (non-Finnish) | 0.00468% | 21,364 |
| East Asian | 0.00223% | 44,766 |
| Admixed American | 0.00171% | 58,512 |
| South Asian | 0.00111% | 90,248 |
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.Ser2650=
- Coding
- c.7950G>A
- MANE Select
- NM_001388492
- Type
- single nucleotide variant
- Location
- chr4:3228716 (GRCh38)
- Structure
- AlphaFold pLDDT 85.38 · 30 PDB
Similar variants
- HTT p.Ser2650Leu 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-ser2650 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown