Is HTT p.Ile2592= (c.7776C>T) pathogenic?

HTT p.Ile2592= (c.7776C>T) is classified Likely benign in HTT (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-16). Very rare (popmax 0.0022%, sas); Associated with HTT-related disorder.

What condition is associated with HTT p.Ile2592= (c.7776C>T)?

HTT p.Ile2592= (c.7776C>T) is associated with HTT-related disorder (ClinVar).

How common is HTT p.Ile2592= (c.7776C>T) in the general population?

HTT p.Ile2592= (c.7776C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

HTT p.Ile2592=

c.7776C>T · rs2474067696 · VCV3032380

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Conditions

HTT-related disorder

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 2.7	GERP 1.5, phastCons 1
Overall
CADD	11.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,086 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000136%

Overall 0.000137% 2/1,461,754 alleles · very rare

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.Ile2592=
Coding: c.7776C>T
MANE Select: NM_001045 · reported on NM_001388492
dbSNP: rs2474067696
Type: single nucleotide variant
Location: chr4:3225671 (GRCh38)
Structure: AlphaFold pLDDT 85.38 · 30 PDB

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

Disease context

HTT-related disorder

Similar variants

HTT p.Phe1142= Likely benign ★★ same condition
HTT p.Pro2946= Likely benign ★★ same condition
HTT p.Val2008= Likely benign ★★ same condition
HTT p.Ala1089= Benign ★ same condition
HTT p.Ala2022= Likely benign ★ same condition
HTT p.Ala229Val Likely benign ★ same condition
HTT p.Ala2338= Likely benign ★ same condition
HTT p.Ala2644= Benign ★ 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-ile2592 (accessed [today's date]).

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