Is HTT p.Arg1303Gln (c.3908G>A) pathogenic?

HTT p.Arg1303Gln (c.3908G>A) is classified Uncertain significance in HTT (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-17). AlphaMissense: likely benign (0.1124); Very rare (popmax 0.00333%, amr).

How common is HTT p.Arg1303Gln (c.3908G>A) in the general population?

HTT p.Arg1303Gln (c.3908G>A) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about HTT p.Arg1303Gln (c.3908G>A)?

AlphaMissense predicts likely benign (score 0.1124) — an in-silico prediction, not a clinical call.

HTT p.Arg1303Gln

c.3908G>A · rs1472029279 · VCV1345302

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1124 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Computational evidence

Protein change
AlphaMissense	0.1124	likely benign
REVEL	0.378	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.1, 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 0.00333% Admixed American · 2/60,002 alleles

Filtering AF 0.00115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000972%

Overall 0.00149% 24/1,611,350 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,001
European (non-Finnish)	0.00178%	56,077
African / African-American	0.00134%	74,814

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.Arg1303Gln
Coding: c.3908G>A
MANE Select: NM_001045 · reported on NM_001388492
dbSNP: rs1472029279
Type: single nucleotide variant
Location: chr4:3172363 (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-arg1303gln (accessed [today's date]).

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