Is TFAP2A p.Pro51Arg (c.152C>G) pathogenic?

TFAP2A p.Pro51Arg (c.152C>G) is classified Uncertain significance in TFAP2A (ClinVar, Single submitter, 1 submitter; last evaluated 2026-06-03). AlphaMissense: likely pathogenic (0.8937); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with TFAP2A p.Pro51Arg (c.152C>G)?

TFAP2A p.Pro51Arg (c.152C>G) is associated with Inborn genetic diseases (ClinVar).

How common is TFAP2A p.Pro51Arg (c.152C>G) in the general population?

TFAP2A p.Pro51Arg (c.152C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TFAP2A p.Pro51Arg (c.152C>G)?

AlphaMissense predicts likely pathogenic (score 0.8937) — an in-silico prediction, not a clinical call.

TFAP2A p.Pro51Arg

c.152C>G · VCV4865628

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8937 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8937	likely pathogenic
REVEL	0.732	pathogenic-leaning
SaProt	LLR -7.65	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 10 kb · p 0.045 · 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 P49R vs ClinVar P51R) — 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.Pro51Arg
Coding: c.152C>G
MANE Select: NM_001372066
Type: single nucleotide variant
Location: chr6:10410235 (GRCh38)
Gene constraint: LOEUF 0.334 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 67.76 · 3 PDB
Residue 49 UniProt numbering: the 'disordered' region

Full TFAP2A 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

TFAP2A p.Pro51Ala Uncertain significance ★ ⚠ same residue
TFAP2A p.Pro51Leu Uncertain significance ★ ⚠ same residue
TFAP2A p.Ala258Val Pathogenic/Likely pathogenic ★★ same condition
TFAP2A p.Arg239Gln Pathogenic/Likely pathogenic ★★ same condition
TFAP2A p.His386Tyr Likely pathogenic ★★ same condition
TFAP2A p.Asn287Ser Uncertain significance ★★ ⚠ same condition
TFAP2A p.Asn367His Uncertain significance ★★ ⚠ same condition
TFAP2A p.Gly108Arg 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/tfap2a-p-pro51arg (accessed [today's date]).

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