Is TFAP2A p.Pro243= (c.729C>G) pathogenic?

TFAP2A p.Pro243= (c.729C>G) is classified Likely benign in TFAP2A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-24). Ultra-rare (popmax 0.036%, afr).

How common is TFAP2A p.Pro243= (c.729C>G) in the general population?

TFAP2A p.Pro243= (c.729C>G) is ultra-rare (popmax 0.036%, afr) (gnomAD).

TFAP2A p.Pro243=

c.729C>G · rs140905560 · VCV738194

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.036%, afr)

⚠ 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.
REVEL	0.681	pathogenic-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -2.6	GERP -4
Overall
CADD	12.78	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.036% African / African-American · 27/75,060 alleles

Filtering AF 0.0254% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0218%

Overall 0.00514% 83/1,613,566 alleles · ultra-rare exomes 60/1,461,252 · genomes 23/152,314 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.036%	2,780
Remaining individualsnot grpmax-eligible	0.0336%	2,974
East Asian	0.029%	3,449
South Asian	0.0231%	4,335
European (non-Finnish)	8.48e-05%	1,179,796

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: TFAP2A
Protein: p.Pro243=
Coding: c.729C>G
MANE Select: NM_001372066
dbSNP: rs140905560
Type: single nucleotide variant
Location: chr6:10404549 (GRCh38)

Full TFAP2A 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/tfap2a-p-pro243 (accessed [today's date]).

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