Is TFAP2A p.Ser144Pro (c.430T>C) pathogenic?

TFAP2A p.Ser144Pro (c.430T>C) is classified Uncertain significance in TFAP2A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-09). AlphaMissense: likely benign (0.0963); Very rare (popmax 0.00527%, nfe); Associated with branchiooculofacial syndrome.

What condition is associated with TFAP2A p.Ser144Pro (c.430T>C)?

TFAP2A p.Ser144Pro (c.430T>C) is associated with branchiooculofacial syndrome (ClinVar).

How common is TFAP2A p.Ser144Pro (c.430T>C) in the general population?

TFAP2A p.Ser144Pro (c.430T>C) is very rare (popmax 0.00527%, nfe) (gnomAD).

What do computational predictors say about TFAP2A p.Ser144Pro (c.430T>C)?

AlphaMissense predicts likely benign (score 0.0963) — an in-silico prediction, not a clinical call.

TFAP2A p.Ser144Pro

c.430T>C · rs1009464114 · VCV2636042

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0963 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00527%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

branchiooculofacial syndrome

Computational evidence

Protein change
AlphaMissense	0.0963	likely benign
REVEL	0.442	indeterminate
SaProt	LLR -6.98	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8	GERP -0.83, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 10 kb · p 0.045 · regional, not allelic
Overall
CADD	23.1	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 S142P vs ClinVar S144P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00527% European (non-Finnish) · 61/1,158,530 alleles

Filtering AF 0.00418% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00379%

Overall 0.00401% 63/1,571,312 alleles · very rare exomes 58/1,419,752 · genomes 5/151,560 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00527%	18,992
Admixed American	0.0019%	52,760
Remaining individualsnot grpmax-eligible	0.00164%	60,934

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.Ser144Pro
Coding: c.430T>C
MANE Select: NM_001372066
dbSNP: rs1009464114
Type: single nucleotide variant
Location: chr6:10409957 (GRCh38)
Gene constraint: LOEUF 0.334 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 67.76 · 3 PDB

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.Ser144= Likely benign ★ same residue
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

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-ser144pro (accessed [today's date]).

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