HTT p.Leu2719=
c.8157G>A · rs2276881 · VCV2167059
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 35.2%, eas) — 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 · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 8.5 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 10.25 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
35.2%
East Asian · 15,776/44,862 alleles
Filtering AF
34.7%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 34.5%
Overall
8.6%
138,865/1,613,994 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 35.2% | 3 |
| Admixed American | 19.4% | 5 |
| South Asian | 16.1% | 6 |
| Remaining individualsnot grpmax-eligible | 9.55% | 10 |
| European (non-Finnish) | 7.14% | 14 |
| Middle Eastern | 6.38% | 16 |
| Ashkenazi Jewishnot grpmax-eligible | 6.36% | 16 |
| Finnishnot grpmax-eligible | 4.99% | 20 |
| African / African-American | 1.46% | 68 |
| Amishnot grpmax-eligible | 1.43% | 70 |
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.Leu2719=
- Coding
- c.8157G>A
- MANE Select
- NM_001045 · reported on NM_001388492
- dbSNP
- rs2276881
- Type
- single nucleotide variant
- Location
- chr4:3229934 (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-leu2719 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown