Is TFAP2B p.Pro34Ser (c.100C>T) pathogenic?

TFAP2B p.Pro34Ser (c.100C>T) is classified Uncertain significance in TFAP2B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-23). AlphaMissense: likely benign (0.074); Very rare (popmax 0.000596%, nfe).

How common is TFAP2B p.Pro34Ser (c.100C>T) in the general population?

TFAP2B p.Pro34Ser (c.100C>T) is very rare (popmax 0.000596%, nfe) (gnomAD).

What do computational predictors say about TFAP2B p.Pro34Ser (c.100C>T)?

AlphaMissense predicts likely benign (score 0.074) — an in-silico prediction, not a clinical call.

TFAP2B p.Pro34Ser

c.100C>T · VCV4892240

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.074 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000596%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.074	likely benign
REVEL	0.18	moderately benign-leaning
SaProt	LLR -5.45	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.3, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 17 kb · p 0.49 · regional, not allelic
Overall
CADD	19.73	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 0.000596% European (non-Finnish) · 7/1,173,780 alleles

Filtering AF 0.000248% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00016%

Overall 0.000437% 7/1,600,156 alleles · very rare exomes 6/1,448,110 · genomes 1/152,046 · 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.Pro34Ser
Coding: c.100C>T
MANE Select: NM_003221
Type: single nucleotide variant
Location: chr6:50823425 (GRCh38)
Gene constraint: LOEUF 0.353 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 65.95 · 1 PDB
Residue 34: the 'disordered' region

Full TFAP2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TFAP2B p.Arg236His Likely pathogenic ★★ same type
TFAP2B p.Arg285Gln Pathogenic/Likely pathogenic ★★ same type
TFAP2B p.Ala54Gly Uncertain significance ★★ same type
TFAP2B p.Asp31Gly Uncertain significance ★★ ⚠ same type
TFAP2B p.Asp346Glu Uncertain significance ★★ same type
TFAP2B p.Pro205Ser Uncertain significance ★★ ⚠ same type
TFAP2B p.Ser277Trp Uncertain significance ★★ ⚠ same type
TFAP2B p.Thr306Met Uncertain significance ★★ ⚠ same type

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-pro34ser (accessed [today's date]).

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