Is TFAP2A p.Pro91Ser (c.271C>T) pathogenic?

TFAP2A p.Pro91Ser (c.271C>T) is classified Uncertain significance in TFAP2A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-08). AlphaMissense: likely benign (0.0962); No allele count reported in gnomAD v4.1 (AN 1,612,806); Associated with branchiooculofacial syndrome.

What condition is associated with TFAP2A p.Pro91Ser (c.271C>T)?

TFAP2A p.Pro91Ser (c.271C>T) is associated with branchiooculofacial syndrome (ClinVar).

How common is TFAP2A p.Pro91Ser (c.271C>T) in the general population?

TFAP2A p.Pro91Ser (c.271C>T) is no allele count reported in gnomAD v4.1 (AN 1,612,806) (gnomAD).

What do computational predictors say about TFAP2A p.Pro91Ser (c.271C>T)?

AlphaMissense predicts likely benign (score 0.0962) — an in-silico prediction, not a clinical call.

TFAP2A p.Pro91Ser

c.271C>T · VCV3592853

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0962 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,612,806)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

branchiooculofacial syndrome

Computational evidence

Protein change
AlphaMissense	0.0962	likely benign
REVEL	0.343	indeterminate
SaProt	LLR -6.41	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 10 kb · p 0.045 · regional, not allelic
Overall
CADD	26.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P89S vs ClinVar P91S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,612,806). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TFAP2A
Protein: p.Pro91Ser
Coding: c.271C>T
MANE Select: NM_001372066
Type: single nucleotide variant
Location: chr6:10410116 (GRCh38)
Gene constraint: LOEUF 0.334 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 67.76 · 3 PDB
Residue 89 UniProt numbering: the 'disordered' region

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

Similar variants

TFAP2A p.Ala258Val Pathogenic/Likely pathogenic ★★ same condition
TFAP2A p.Arg239Gln Pathogenic/Likely pathogenic ★★ same condition
TFAP2A p.Arg325Ter Pathogenic ★★ same condition
TFAP2A p.Gln32Ter Likely pathogenic ★★ same condition
TFAP2A p.Glu235Lys Likely pathogenic ★★ same condition
TFAP2A p.Asn287Ser Uncertain significance ★★ ⚠ same condition
TFAP2A p.Asp329Asn Uncertain significance ★★ same condition
TFAP2A p.Pro81Ala 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-pro91ser (accessed [today's date]).

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