Is THAP1 p.Pro103Arg (c.308C>G) pathogenic?

THAP1 p.Pro103Arg (c.308C>G) is classified Uncertain significance in THAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-05). AlphaMissense: likely benign (0.1018); Very rare (popmax 8.48e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with THAP1 p.Pro103Arg (c.308C>G)?

THAP1 p.Pro103Arg (c.308C>G) is associated with Inborn genetic diseases (ClinVar).

How common is THAP1 p.Pro103Arg (c.308C>G) in the general population?

THAP1 p.Pro103Arg (c.308C>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about THAP1 p.Pro103Arg (c.308C>G)?

AlphaMissense predicts likely benign (score 0.1018) — an in-silico prediction, not a clinical call.

THAP1 p.Pro103Arg

c.308C>G · VCV4633102

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1018 · ACMG-weighted

gnomAD v4.1

Rare

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

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1018	likely benign
REVEL	0.377	indeterminate
SaProt	LLR -10.29	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 2.3, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 5,129 bp · p 1.3e-06 · regional, not allelic
Overall
CADD	20.5	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 8.48e-05% European (non-Finnish) · 1/1,179,932 alleles

Overall 6.2e-05% 1/1,614,046 alleles · very rare exomes 1/1,461,738 · genomes 0/152,308 · 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.Pro103Arg
Coding: c.308C>G
MANE Select: NM_018105
Type: single nucleotide variant
Location: chr8:42838296 (GRCh38)
Gene constraint: LOEUF 0.571 · pLI 0.90 (gnomAD)
Structure: AlphaFold pLDDT 71.61 · 3 PDB

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.Pro103fs Pathogenic ★ same residue
THAP1 p.Ala115Pro Conflicting classifications of pathogenicity ★ ⚠ same condition
THAP1 p.Asp141Gly 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-pro103arg (accessed [today's date]).

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