HTT p.Leu2399=
c.7195C>T · rs747521327 · VCV1573816
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0507%, 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 0.77 | GERP 1.2, phastCons 0.8 |
| Overall | ||
| CADD | 7.259 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0507%
African / African-American · 38/74,954 alleles
Filtering AF
0.038%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0334%
Overall
0.00297%
48/1,613,478 alleles · ultra-rare
exomes 23/1,461,226 · genomes 25/152,252 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0507% | 1,972 |
| Admixed American | 0.00833% | 11,998 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,492 |
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.Leu2399=
- Coding
- c.7195C>T
- MANE Select
- NM_001388492
- dbSNP
- rs747521327
- Type
- single nucleotide variant
- Location
- chr4:3217905 (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-leu2399 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown