Is HTT p.Ser2027Gly (c.6079A>G) pathogenic?

HTT p.Ser2027Gly (c.6079A>G) is classified Uncertain significance in HTT (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-10). AlphaMissense: likely benign (0.1045); Very rare (popmax 8.48e-05%, nfe).

How common is HTT p.Ser2027Gly (c.6079A>G) in the general population?

HTT p.Ser2027Gly (c.6079A>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about HTT p.Ser2027Gly (c.6079A>G)?

AlphaMissense predicts likely benign (score 0.1045) — an in-silico prediction, not a clinical call.

HTT p.Ser2027Gly

c.6079A>G · rs2110270279 · VCV1420637

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1045 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.1045	likely benign
REVEL	0.218	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	Δ0.80	acceptor loss, 2 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 5.3	GERP 1.8, phastCons 1
Overall
CADD	21.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,802 alleles

Overall 6.84e-05% 1/1,461,474 alleles · very rare

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.Ser2027Gly
Coding: c.6079A>G
MANE Select: NM_001045 · reported on NM_001388492
dbSNP: rs2110270279
Type: single nucleotide variant
Location: chr4:3207284 (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-ser2027gly (accessed [today's date]).

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