Is TFAP2A p.Arg239Pro (c.716G>C) pathogenic?

TFAP2A p.Arg239Pro (c.716G>C) is classified Pathogenic in TFAP2A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-03-11). AlphaMissense: likely pathogenic (0.9997); Absent from gnomAD v4.1; Associated with branchiooculofacial syndrome.

What condition is associated with TFAP2A p.Arg239Pro (c.716G>C)?

TFAP2A p.Arg239Pro (c.716G>C) is associated with branchiooculofacial syndrome (ClinVar).

How common is TFAP2A p.Arg239Pro (c.716G>C) in the general population?

TFAP2A p.Arg239Pro (c.716G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TFAP2A p.Arg239Pro (c.716G>C)?

AlphaMissense predicts likely pathogenic (score 0.9997) — an in-silico prediction, not a clinical call.

TFAP2A p.Arg239Pro

c.716G>C · rs151344525 · VCV547798

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9997 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

branchiooculofacial syndrome

Computational evidence

Protein change
AlphaMissense	0.9997	likely pathogenic ✓ concordant with ClinVar
REVEL	0.969	strongly pathogenic-leaning
SaProt	LLR -12.49	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.5	GERP 2, phastCons 1
Regional constraint	o/e 0.44	unconstrained · MANE · 4,122 bp · p 5.2e-11 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R237P vs ClinVar R239P) — verify the residue.

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: TFAP2A
Protein: p.Arg239Pro
Coding: c.716G>C
dbSNP: rs151344525
Type: single nucleotide variant
Location: chr6:10404562 (GRCh38)

Full TFAP2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

branchiooculofacial syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-arg239pro (accessed [today's date]).

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