Is THAP1 p.Thr48Ser (c.143C>G) pathogenic?

THAP1 p.Thr48Ser (c.143C>G) is classified Uncertain significance in THAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-01). AlphaMissense: likely benign (0.2999); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with THAP1 p.Thr48Ser (c.143C>G)?

THAP1 p.Thr48Ser (c.143C>G) is associated with Inborn genetic diseases (ClinVar).

How common is THAP1 p.Thr48Ser (c.143C>G) in the general population?

THAP1 p.Thr48Ser (c.143C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about THAP1 p.Thr48Ser (c.143C>G)?

AlphaMissense predicts likely benign (score 0.2999) — an in-silico prediction, not a clinical call.

THAP1 p.Thr48Ser

c.143C>G · rs1802673290 · VCV3176871

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2999 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2999	likely benign
REVEL	0.351	indeterminate
SaProt	LLR -6.13	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.5	GERP 2.4, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 5,129 bp · p 1.3e-06 · regional, not allelic
Overall
CADD	21.8	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 and SaProt are independent agreement signals.

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: THAP1
Protein: p.Thr48Ser
Coding: c.143C>G
MANE Select: NM_018105
dbSNP: rs1802673290
Type: single nucleotide variant
Location: chr8:42839310 (GRCh38)
Gene constraint: LOEUF 0.571 · pLI 0.90 (gnomAD)
Structure: AlphaFold pLDDT 71.61 · 3 PDB
Residue 48: a turn

Full THAP1 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

THAP1 p.Arg29Pro Pathogenic/Likely pathogenic ★★ same condition
THAP1 p.Met120Val Uncertain significance ★★ ⚠ same condition
THAP1 p.Thr125Pro Uncertain significance ★★ ⚠ same condition
THAP1 p.Val183Phe Uncertain significance ★★ ⚠ same condition
THAP1 p.Thr165= Likely benign ★★ same condition
THAP1 p.Ala115Pro Conflicting classifications of pathogenicity ★ ⚠ same condition
THAP1 p.Asp141Gly Uncertain significance ★ ⚠ same condition
THAP1 p.Cys83Phe 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/thap1-p-thr48ser (accessed [today's date]).

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