HTT p.Thr2654=
c.7962G>A · rs369624996 · VCV3238955
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00632%, nfe)
Conditions
1
Lopes-Maciel-Rodan syndrome
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 -5.2 | GERP -3.8 |
| Overall | ||
| CADD | 1.299 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00632%
European (non-Finnish) · 74/1,170,118 alleles
Filtering AF
0.00515%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00472%
Overall
0.00547%
79/1,442,952 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00632% | 15,812 |
| African / African-American | 0.00405% | 24,710 |
| East Asian | 0.00224% | 44,642 |
| Remaining individualsnot grpmax-eligible | 0.00163% | 61,538 |
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.Thr2654=
- Coding
- c.7962G>A
- MANE Select
- NM_001045 · reported on NM_001388492
- dbSNP
- rs369624996
- Type
- single nucleotide variant
- Location
- chr4:3228728 (GRCh38)
- Structure
- AlphaFold pLDDT 85.38 · 30 PDB
Similar variants
- HTT p.Asp920Asn Uncertain significance ★★ same condition
- HTT p.Gly2968Asp Uncertain significance ★★ same condition
- HTT p.Leu1237Ile Uncertain significance ★★ ⚠ same condition
- HTT p.Pro703Leu Uncertain significance ★★ ⚠ same condition
- HTT c.7765+10G>A Benign/Likely benign ★★ same condition
- HTT p.Thr1260Met Benign ★★ same condition
- HTT p.Val1546= Benign/Likely benign ★★ same condition
- HTT p.Leu2307= Likely pathogenic ★ same condition
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-thr2654 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown