Is HTT p.Asp920Asn (c.2758G>A) pathogenic?

HTT p.Asp920Asn (c.2758G>A) is classified Uncertain significance in HTT (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-08-01). AlphaMissense: likely pathogenic (0.9239); Ultra-rare (popmax 0.0891%, nfe); Associated with Lopes-Maciel-Rodan syndrome.

What condition is associated with HTT p.Asp920Asn (c.2758G>A)?

HTT p.Asp920Asn (c.2758G>A) is associated with Lopes-Maciel-Rodan syndrome, Huntington disease (ClinVar).

How common is HTT p.Asp920Asn (c.2758G>A) in the general population?

HTT p.Asp920Asn (c.2758G>A) is ultra-rare (popmax 0.0891%, nfe) (gnomAD).

What do computational predictors say about HTT p.Asp920Asn (c.2758G>A)?

AlphaMissense predicts likely pathogenic (score 0.9239) — an in-silico prediction, not a clinical call.

HTT p.Asp920Asn

c.2758G>A · rs80100842 · VCV1298952

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9239 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0891%, nfe)

Conditions

Lopes-Maciel-Rodan syndrome

Computational evidence

Protein change
AlphaMissense	0.9239	likely pathogenic
REVEL	0.467	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 2.2, phastCons 1
Overall
CADD	29.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0891% European (non-Finnish) · 1,050/1,177,996 alleles

Filtering AF 0.0846% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0828%

Overall 0.0673% 1,085/1,611,710 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0891%	1,122
Remaining individualsnot grpmax-eligible	0.0336%	2,973
African / African-American	0.012%	8,326
Finnishnot grpmax-eligible	0.00781%	12,799

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.Asp920Asn
Coding: c.2758G>A
MANE Select: NM_001045 · reported on NM_001388492
dbSNP: rs80100842
Type: single nucleotide variant
Location: chr4:3136286 (GRCh38)
Structure: AlphaFold pLDDT 85.38 · 30 PDB

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

Disease context

Lopes-Maciel-Rodan syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Huntington disease

Similar variants

HTT p.Gly2084Arg Uncertain significance ★★ same condition
HTT p.Gly2968Asp Uncertain significance ★★ same condition
HTT p.Leu1237Ile Uncertain significance ★★ ⚠ same condition
HTT p.Pro703Leu Uncertain significance ★★ ⚠ same condition
HTT p.Val2500Ile Uncertain significance ★★ ⚠ same condition
HTT c.7765+10G>A Benign/Likely benign ★★ same condition
HTT p.Thr1260Met Benign ★★ same condition
HTT p.Val1546= Benign/Likely 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-asp920asn (accessed [today's date]).

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