HTT p.Glu2643del
c.7919AGG[3] · rs149109767 · VCV1599428
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 12.1%, amr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.1 | GERP -3.8, phastCons 0.14 |
| Overall | ||
| CADD | 18.62 | PHRED · no single calibrated threshold — expert panels disagree |
| Region caveats | ||
| Repeat context | tandem | GA-rich low complexity · ambiguous alignment · confidence, not pathogenicity |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
12.1%
Admixed American · 7,166/59,352 alleles
Filtering AF
11.8%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 11.7%
Overall
6.56%
105,647/1,610,112 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 12.1% | 8 |
| European (non-Finnish) | 7.37% | 14 |
| Finnishnot grpmax-eligible | 6.57% | 15 |
| Remaining individualsnot grpmax-eligible | 5.72% | 17 |
| Ashkenazi Jewishnot grpmax-eligible | 2.52% | 40 |
| South Asian | 2.28% | 44 |
| Amishnot grpmax-eligible | 1.54% | 65 |
| Middle Eastern | 1.43% | 70 |
| African / African-American | 1.39% | 72 |
| East Asian | 0.0268% | 3,737 |
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.Glu2643del
- Coding
- c.7919AGG[3]
- MANE Select
- NM_001045 · reported on NM_001388492
- dbSNP
- rs149109767
- Type
- Microsatellite
- Location
- chr4:3228684 (GRCh38)
- Structure
- AlphaFold pLDDT 85.38 · 30 PDB
Similar variants
- HTT p.Gln31_Gln38dup Benign/Likely benign ★★ same type
- HTT p.Gln32_Gln38dup Benign/Likely benign ★★ same type
- HTT p.Gln33_Gln38dup Benign/Likely benign ★★ same type
- HTT p.Gln34_Gln38del Likely benign ★★ same type
- HTT p.Gln36_Gln38del Benign/Likely benign ★★ same type
- HTT p.Gln38_Pro39insGln Benign ★★ same type
- HTT p.Gln38_Pro39insGlnGlnGlnGlnGln Likely benign ★★ same type
- HTT p.Gln38_Pro39insGlnGlnGlnGlnGlnGlnGlnGlnGln Likely benign ★★ 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-glu2643del (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown