HTT p.Ile2817=
c.8451C>T · rs1239696454 · VCV1626800
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00412%, nfe)
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 -3.7 | GERP -3.9 |
| Overall | ||
| CADD | 1.512 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00412%
European (non-Finnish) · 48/1,165,522 alleles
Filtering AF
0.00319%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00282%
Overall
0.0032%
51/1,595,490 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00412% | 24,282 |
| Remaining individualsnot grpmax-eligible | 0.00325% | 30,774 |
| South Asian | 0.0011% | 90,524 |
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.Ile2817=
- Coding
- c.8451C>T
- MANE Select
- NM_001045 · reported on NM_001388492
- dbSNP
- rs1239696454
- Type
- single nucleotide variant
- Location
- chr4:3233348 (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-ile2817 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown