Is TFAP2A p.Ser39Phe (c.116C>T) pathogenic?

TFAP2A p.Ser39Phe (c.116C>T) is classified Uncertain significance in TFAP2A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-16). AlphaMissense: ambiguous (0.3845); Very rare (popmax 0.00835%, amr); Associated with branchiooculofacial syndrome.

What condition is associated with TFAP2A p.Ser39Phe (c.116C>T)?

TFAP2A p.Ser39Phe (c.116C>T) is associated with branchiooculofacial syndrome (ClinVar).

How common is TFAP2A p.Ser39Phe (c.116C>T) in the general population?

TFAP2A p.Ser39Phe (c.116C>T) is very rare (popmax 0.00835%, amr) (gnomAD).

What do computational predictors say about TFAP2A p.Ser39Phe (c.116C>T)?

AlphaMissense predicts ambiguous (score 0.3845) — an in-silico prediction, not a clinical call.

TFAP2A p.Ser39Phe

c.116C>T · rs779448987 · VCV1918881

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3845 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00835%, amr)

Conditions

branchiooculofacial syndrome

Computational evidence

Protein change
AlphaMissense	0.3845	ambiguous
REVEL	0.509	indeterminate
SaProt	LLR -8.74	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.4	GERP -2.4, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 10 kb · p 0.045 · regional, not allelic
Overall
CADD	33.0	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 S37F vs ClinVar S39F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00835% Admixed American · 5/59,880 alleles

Filtering AF 0.00324% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.00031% 5/1,612,188 alleles · very rare exomes 4/1,461,376 · genomes 1/150,812 · joint denominator

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.Ser39Phe
Coding: c.116C>T
MANE Select: NM_001372066
dbSNP: rs779448987
Type: single nucleotide variant
Location: chr6:10410271 (GRCh38)
Gene constraint: LOEUF 0.334 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 67.76 · 3 PDB
Residue 37 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-ser39phe (accessed [today's date]).

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