HTT p.Gln34fs
c.99_100del · rs1560534953 · VCV1809691
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function; NMD-escape possible for C-terminal truncations |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 1.4 | GERP -0.5, phastCons 1 |
| Overall | ||
| CADD | 20.6 | PHRED · no single calibrated threshold — expert panels disagree |
| Region caveats | ||
| Repeat context | tandem | (CAG)n simple repeat · ambiguous alignment · confidence, not pathogenicity |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Finnishnot grpmax-eligible | 0.161% | 623 |
| African / African-Americangrpmax | 0.141% | 709 |
| South Asian | 0.0581% | 1,722 |
| Remaining individualsnot grpmax-eligible | 0.0396% | 2,524 |
| European (non-Finnish) | 0.0299% | 3,348 |
| Middle Eastern | 0.0231% | 4,330 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0184% | 5,448 |
| Admixed American | 0.0166% | 6,036 |
| East Asian | 0.0163% | 6,125 |
Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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.Gln34fs
- Coding
- c.99_100del
- MANE Select
- NM_001388492
- dbSNP
- rs1560534953
- Type
- Deletion
- Location
- chr4:3074918 (GRCh38)
- Structure
- AlphaFold pLDDT 85.38 · 30 PDB
- Residue 34
- the 'disordered' region
Disease context
Huntington disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: Lopes-Maciel-Rodan syndrome
For Huntington disease (Orphanet):
- Inheritance
- Autosomal dominant
- Onset
- Adolescent, Adult, Childhood, Elderly
- Prevalence
- 1-9 / 100 000 (Greece)
Similar variants
- HTT p.Gln34_Gln38del Likely benign ★★ same residue
- HTT p.Gln33fs Likely pathogenic ★ same condition
- HTT p.Gln33_Gln38del Likely benign ★ same condition
- HTT p.Asp920Asn Uncertain significance ★★ same condition
- HTT p.Gly2084Arg 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
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-gln34fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown