Is HTT p.Asp2009Asn (c.6025G>A) pathogenic?

HTT p.Asp2009Asn (c.6025G>A) is classified Uncertain significance in HTT (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-11). AlphaMissense: likely pathogenic (0.5984); Ultra-rare (popmax 0.0891%, eas).

How common is HTT p.Asp2009Asn (c.6025G>A) in the general population?

HTT p.Asp2009Asn (c.6025G>A) is ultra-rare (popmax 0.0891%, eas) (gnomAD).

What do computational predictors say about HTT p.Asp2009Asn (c.6025G>A)?

AlphaMissense predicts likely pathogenic (score 0.5984) — an in-silico prediction, not a clinical call.

HTT p.Asp2009Asn

c.6025G>A · rs773337081 · VCV1397228

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5984 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0891%, eas)

Missense predictors

1/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.5984	likely pathogenic
REVEL	0.252	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense calls this damaging; REVEL does not; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 0.91, phastCons 1
Overall
CADD	26.8	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 0.0891% East Asian · 40/44,892 alleles

Filtering AF 0.0673% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0596%

Overall 0.00397% 64/1,613,850 alleles · ultra-rare exomes 61/1,461,714 · genomes 3/152,136 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0891%	1,122
Remaining individualsnot grpmax-eligible	0.0032%	31,242
European (non-Finnish)	0.00178%	56,189
Admixed American	0.00167%	59,966

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.Asp2009Asn
Coding: c.6025G>A
MANE Select: NM_001388492
dbSNP: rs773337081
Type: single nucleotide variant
Location: chr4:3206933 (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-asp2009asn (accessed [today's date]).

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