Is TFAP2A p.Ser293fs (c.875dup) pathogenic?

TFAP2A p.Ser293fs (c.875dup) is classified Pathogenic in TFAP2A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-18). Associated with TFAP2A-related disorder.

What condition is associated with TFAP2A p.Ser293fs (c.875dup)?

TFAP2A p.Ser293fs (c.875dup) is associated with TFAP2A-related disorder (ClinVar).

TFAP2A p.Ser293fs

c.875dup · VCV4973669

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

TFAP2A-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 5 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -3.5	GERP -4

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: TFAP2A
Protein: p.Ser293fs
Coding: c.875dup
MANE Select: NM_001372066
Type: Duplication
Location: chr6:10402505 (GRCh38)
Gene constraint: LOEUF 0.334 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 67.76 · 3 PDB
Residue 293: the 'h-s-h (helix-span-helix), dimerization' region

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

Disease context

TFAP2A-related disorder

Similar variants

TFAP2A p.Ser293Pro Uncertain significance ★ ⚠ same residue
TFAP2A p.Gly263Ter Likely pathogenic ★ same condition
TFAP2A p.Ile158Met Conflicting classifications of pathogenicity ★ ⚠ same condition
TFAP2A p.Leu271Arg Uncertain significance ★ ⚠ same condition
TFAP2A c.52-1249A>G Uncertain significance same condition
TFAP2A p.Leu109Arg Uncertain significance ⚠ same condition
TFAP2A p.Thr424Met Uncertain significance ⚠ same condition
TFAP2A p.Tyr403Ter 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-ser293fs (accessed [today's date]).

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