HTT p.Glu2734=
c.8202A>G · rs200586785 · VCV1568347
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.028%, 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 -2.8 | GERP -3.7 |
| Overall | ||
| CADD | 1.098 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.028%
African / African-American · 21/75,048 alleles
Filtering AF
0.0187%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0157%
Overall
0.00142%
23/1,614,074 alleles · ultra-rare
exomes 12/1,461,764 · genomes 11/152,310 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.028% | 3,574 |
| Admixed American | 0.00333% | 30,011 |
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.Glu2734=
- Coding
- c.8202A>G
- MANE Select
- NM_001388492
- dbSNP
- rs200586785
- Type
- single nucleotide variant
- Location
- chr4:3229979 (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-glu2734 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown