HTT p.Pro49dup
c.123GCC[8] · rs772429544 · VCV599433
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0461%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -6.2 | GERP -0.67 |
| Overall | ||
| CADD | 7.344 | PHRED · no single calibrated threshold — expert panels disagree |
| Region caveats | ||
| Repeat context | tandem | (CGC)n simple repeat · ambiguous alignment · confidence, not pathogenicity |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0461%
East Asian · 15/32,546 alleles
Filtering AF
0.0311%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0264%
Overall
0.0197%
239/1,214,690 alleles · ultra-rare
exomes 218/1,089,052 · genomes 21/125,638 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0461% | 2,170 |
| African / African-American | 0.0451% | 2,217 |
| Middle Eastern | 0.0268% | 3,734 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0212% | 4,723 |
| South Asian | 0.0191% | 5,230 |
| Remaining individualsnot grpmax-eligible | 0.0186% | 5,372 |
| European (non-Finnish) | 0.0181% | 5,528 |
| Admixed American | 0.0153% | 6,536 |
| Finnishnot grpmax-eligible | 0.00514% | 19,455 |
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.Pro49dup
- Coding
- c.123GCC[8]
- MANE Select
- NM_001388492
- dbSNP
- rs772429544
- Type
- Microsatellite
- Location
- chr4:3074945 (GRCh38)
- Structure
- AlphaFold pLDDT 85.38 · 30 PDB
- Residue 49
- the 'disordered' region
Similar variants
- HTT p.Pro49_Gln50insProProPro Benign ★ same residue
- HTT p.Pro49_Gln50insProProProPro Likely benign ★ same residue
- HTT p.Pro49_Gln50insProProProProPro Likely benign ★ same residue
- HTT p.Pro49_Gln50insProPro Likely benign ★ same residue
- HTT p.Gln31_Gln38dup Benign/Likely benign ★★ same type
- HTT p.Gln32_Gln38dup Benign/Likely benign ★★ same type
- HTT p.Gln33_Gln38dup Benign/Likely benign ★★ same type
- HTT p.Gln34_Gln38del Likely benign ★★ 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-pro49dup (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown