Is THAP1 p.Val183Ala (c.548T>C) pathogenic?

THAP1 p.Val183Ala (c.548T>C) is classified Uncertain significance in THAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-03). AlphaMissense: likely benign (0.0942); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with THAP1 p.Val183Ala (c.548T>C)?

THAP1 p.Val183Ala (c.548T>C) is associated with Inborn genetic diseases (ClinVar).

How common is THAP1 p.Val183Ala (c.548T>C) in the general population?

THAP1 p.Val183Ala (c.548T>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about THAP1 p.Val183Ala (c.548T>C)?

AlphaMissense predicts likely benign (score 0.0942) — an in-silico prediction, not a clinical call.

THAP1 p.Val183Ala

c.548T>C · VCV3456011

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0942 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0942	likely benign
REVEL	0.174	moderately benign-leaning
SaProt	LLR -6.80	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP -1.3, phastCons 0.97
Regional constraint	o/e 0.70	unconstrained · MANE · 5,129 bp · p 1.3e-06 · regional, not allelic
Overall
CADD	14.91	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

Grpmax group 0.00167% Admixed American · 1/59,940 alleles

Overall 6.2e-05% 1/1,613,828 alleles · very rare exomes 1/1,461,730 · genomes 0/152,098 · joint denominator

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: THAP1
Protein: p.Val183Ala
Coding: c.548T>C
MANE Select: NM_018105
Type: single nucleotide variant
Location: chr8:42838056 (GRCh38)
Gene constraint: LOEUF 0.571 · pLI 0.90 (gnomAD)
Structure: AlphaFold pLDDT 71.61 · 3 PDB
Residue 183: the 'involved in homodimer formation' region

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.Val183Phe Uncertain significance ★★ ⚠ same residue
THAP1 p.Arg29Pro Pathogenic/Likely pathogenic ★★ same condition
THAP1 p.Met120Val Uncertain significance ★★ ⚠ same condition
THAP1 p.Thr125Pro 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-val183ala (accessed [today's date]).

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