Is THAP11 p.Pro27= (c.81A>C) pathogenic?

THAP11 p.Pro27= (c.81A>C) is classified Uncertain significance in THAP11 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-04). Very rare (popmax 0.00243%, eas).

How common is THAP11 p.Pro27= (c.81A>C) in the general population?

THAP11 p.Pro27= (c.81A>C) is very rare (popmax 0.00243%, eas) (gnomAD).

THAP11 p.Pro27=

c.81A>C · rs763532068 · VCV2893792

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00243%, eas)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.4	GERP -0.46, phastCons 1
Overall
CADD	14.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00243% East Asian · 1/41,118 alleles

Overall 0.000193% 3/1,553,522 alleles · very rare exomes 2/1,401,398 · genomes 1/152,124 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00243%	41,118
African / African-American	0.00137%	73,108
European (non-Finnish)	8.71e-05%	1,148,179

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: THAP11
Protein: p.Pro27=
Coding: c.81A>C
MANE Select: NM_020457
dbSNP: rs763532068
Type: single nucleotide variant
Location: chr16:67842635 (GRCh38)

Full THAP11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/thap11-p-pro27 (accessed [today's date]).

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