Is HTT p.Glu2444Asp (c.7332A>T) pathogenic?

HTT p.Glu2444Asp (c.7332A>T) is classified Likely benign in HTT (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-07-01). AlphaMissense: likely benign (0.1442); Rare (popmax 0.349%, sas).

How common is HTT p.Glu2444Asp (c.7332A>T) in the general population?

HTT p.Glu2444Asp (c.7332A>T) is rare (popmax 0.349%, sas) (gnomAD).

What do computational predictors say about HTT p.Glu2444Asp (c.7332A>T)?

AlphaMissense predicts likely benign (score 0.1442) — an in-silico prediction, not a clinical call.

HTT p.Glu2444Asp

c.7332A>T · rs201702168 · VCV1617281

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1442 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.349%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.1442	likely benign
REVEL	0.25	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.6	GERP -3.6, phastCons 0.98
Overall
CADD	11.87	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.349% South Asian · 318/91,074 alleles

Filtering AF 0.318% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.305%

Overall 0.201% 3,239/1,614,146 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.349%	286
European (non-Finnish)	0.231%	433
Remaining individualsnot grpmax-eligible	0.154%	651
Admixed American	0.0616%	1,622
Middle Eastern	0.0495%	2,021
Finnishnot grpmax-eligible	0.0406%	2,463
African / African-American	0.04%	2,501
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,803

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.Glu2444Asp
Coding: c.7332A>T
MANE Select: NM_001045 · reported on NM_001388492
dbSNP: rs201702168
Type: single nucleotide variant
Location: chr4:3220271 (GRCh38)
Structure: AlphaFold pLDDT 85.38 · 30 PDB

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

Similar variants

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
HTT p.Glu449Ala Uncertain significance ★★ ⚠ same type
HTT p.Gly2084Arg 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-glu2444asp (accessed [today's date]).

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