Is HTT p.Gln33fs (c.99_102del) pathogenic?

HTT p.Gln33fs (c.99102del) is classified Likely pathogenic in HTT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-05). Absent from gnomAD v4.1; Associated with Huntington disease.

What condition is associated with HTT p.Gln33fs (c.99_102del)?

HTT p.Gln33fs (c.99_102del) is associated with Huntington disease (ClinVar).

How common is HTT p.Gln33fs (c.99_102del) in the general population?

HTT p.Gln33fs (c.99_102del) is absent from gnomAD v4.1 (gnomAD).

How is Huntington disease inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

HTT p.Gln33fs

c.99_102del · VCV3779748

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,493,590)

Conditions

Huntington disease

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
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

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,493,590). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: HTT
Protein: p.Gln33fs
Coding: c.99_102del
MANE Select: NM_001045 · reported on NM_001388492
Type: Deletion
Location: chr4:3074918 (GRCh38)
Structure: AlphaFold pLDDT 85.38 · 30 PDB
Residue 33: the 'disordered' region

Full HTT gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Huntington disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Huntington disease (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood, Elderly
Prevalence: 1-9 / 100 000 (Greece)

Similar variants

HTT p.Gln33_Gln38del Likely benign ★ same residue
HTT p.Gln33_Gln38dup Benign/Likely benign ★★ same residue
HTT p.Gln34fs 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.Pro703Leu Uncertain significance ★★ ⚠ same condition
HTT p.Val2500Ile 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-gln33fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown