Is TFAP2B p.Pro130Ser (c.388C>T) pathogenic?

TFAP2B p.Pro130Ser (c.388C>T) is classified Uncertain significance in TFAP2B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-26). AlphaMissense: likely benign (0.1082); Very rare (popmax 0.000424%, nfe); Associated with Inborn genetic diseases.

What condition is associated with TFAP2B p.Pro130Ser (c.388C>T)?

TFAP2B p.Pro130Ser (c.388C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TFAP2B p.Pro130Ser (c.388C>T) in the general population?

TFAP2B p.Pro130Ser (c.388C>T) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about TFAP2B p.Pro130Ser (c.388C>T)?

AlphaMissense predicts likely benign (score 0.1082) — an in-silico prediction, not a clinical call.

TFAP2B p.Pro130Ser

c.388C>T · VCV3455614

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1082 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1082	likely benign
REVEL	0.34	indeterminate
SaProt	LLR -5.96	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 17 kb · p 0.49 · regional, not allelic
Overall
CADD	24.4	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,179,582 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,613,084 alleles · very rare exomes 5/1,460,782 · genomes 0/152,302 · 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: TFAP2B
Protein: p.Pro130Ser
Coding: c.388C>T
MANE Select: NM_003221
Type: single nucleotide variant
Location: chr6:50823713 (GRCh38)
Gene constraint: LOEUF 0.353 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 65.95 · 1 PDB
Residue 130: the 'disordered' region

Full TFAP2B 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

TFAP2B p.Ala54Gly Uncertain significance ★★ same condition
TFAP2B p.Asp346Glu Uncertain significance ★★ same condition
TFAP2B p.Pro205Ser Uncertain significance ★★ ⚠ same condition
TFAP2B c.601+1G>A Pathogenic ★ same condition
TFAP2B p.Tyr51Ter Pathogenic ★ same condition
TFAP2B p.Ala333Thr Uncertain significance ★ ⚠ same condition
TFAP2B p.Arg29Leu Uncertain significance ★ ⚠ same condition
TFAP2B p.Arg342Gln 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/tfap2b-p-pro130ser (accessed [today's date]).

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