Is HTT p.Thr1720Ser (c.5159C>G) pathogenic?

HTT p.Thr1720Ser (c.5159C>G) is classified Uncertain significance in HTT (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-03). AlphaMissense: likely benign (0.0588); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with HTT p.Thr1720Ser (c.5159C>G)?

HTT p.Thr1720Ser (c.5159C>G) is associated with Inborn genetic diseases (ClinVar).

How common is HTT p.Thr1720Ser (c.5159C>G) in the general population?

HTT p.Thr1720Ser (c.5159C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about HTT p.Thr1720Ser (c.5159C>G)?

AlphaMissense predicts likely benign (score 0.0588) — an in-silico prediction, not a clinical call.

HTT p.Thr1720Ser

c.5159C>G · rs363125 · VCV2263737

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0588 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0588	likely benign
REVEL	0.017	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.2	GERP -4.1
Overall
CADD	0.005	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: HTT
Protein: p.Thr1720Ser
Coding: c.5159C>G
MANE Select: NM_001388492
dbSNP: rs363125
Type: single nucleotide variant
Location: chr4:3187820 (GRCh38)
Structure: AlphaFold pLDDT 85.38 · 30 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

HTT p.Thr1720Asn Benign ★★ same residue
HTT p.Arg416Cys Uncertain significance ★ ⚠ same condition
HTT p.Gln29Pro Uncertain significance ★ ⚠ same condition
HTT p.Gln31Pro Conflicting classifications of pathogenicity ★ ⚠ same condition
HTT p.Gln35Pro Uncertain significance ★ ⚠ same condition
HTT p.Pro3007Leu Uncertain significance ★ same condition
HTT p.Pro41Gln Uncertain significance ★ ⚠ same condition
HTT p.Val1484Glu Uncertain significance ★ 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-thr1720ser (accessed [today's date]).

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