HTT p.Gln37=
c.111G>A · VCV4966125
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 1.05%, 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 1 | GERP 0.14, phastCons 0.2 |
| Overall | ||
| CADD | 5.39 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.05%
African / African-American · 660/63,028 alleles
Filtering AF
0.981%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.955%
Overall
0.108%
1,405/1,302,200 alleles · low-frequency
exomes 886/1,176,422 · genomes 519/125,778 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.05% | 95 |
| Middle Eastern | 0.394% | 254 |
| Finnishnot grpmax-eligible | 0.309% | 324 |
| Remaining individualsnot grpmax-eligible | 0.137% | 731 |
| Admixed American | 0.062% | 1,612 |
| European (non-Finnish) | 0.0496% | 2,017 |
| South Asian | 0.0217% | 4,617 |
| East Asian | 0.0207% | 4,839 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0178% | 5,624 |
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.Gln37=
- Coding
- c.111G>A
- MANE Select
- NM_001388492 · reported on NM_002111
- Type
- single nucleotide variant
- Location
- chr4:3074930 (GRCh38)
- Structure
- AlphaFold pLDDT 85.38 · 30 PDB
- Residue 37
- the 'disordered' region
Similar variants
- HTT p.Gln37_Gln38del Likely benign ★ same residue
- HTT p.Gln37fs Likely benign ★ same residue
- 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
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-gln37 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown