Is HTT p.Gln1872His (c.5616G>C) pathogenic?

HTT p.Gln1872His (c.5616G>C) is classified Likely benign in HTT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-24). AlphaMissense: likely benign (0.1157); Rare (popmax 0.247%, sas).

How common is HTT p.Gln1872His (c.5616G>C) in the general population?

HTT p.Gln1872His (c.5616G>C) is rare (popmax 0.247%, sas) (gnomAD).

What do computational predictors say about HTT p.Gln1872His (c.5616G>C)?

AlphaMissense predicts likely benign (score 0.1157) — an in-silico prediction, not a clinical call.

HTT p.Gln1872His

c.5616G>C · rs377417767 · VCV1375604

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1157 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.247%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.1157	likely benign
REVEL	0.159	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP -0.14, phastCons 1
Overall
CADD	15.29	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 0.247% South Asian · 225/91,084 alleles

Filtering AF 0.221% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.21%

Overall 0.0165% 266/1,614,150 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.247%	405
Remaining individualsnot grpmax-eligible	0.0048%	20,833
European (non-Finnish)	0.00322%	31,052

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.Gln1872His
Coding: c.5616G>C
MANE Select: NM_001045 · reported on NM_001388492
dbSNP: rs377417767
Type: single nucleotide variant
Location: chr4:3204046 (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-gln1872his (accessed [today's date]).

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