TFAP2B p.Pro174=
c.522C>G · rs886061565 · VCV357276
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00217%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -6.8 | GERP -4.2 |
| Overall | ||
| CADD | 7.476 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00217%
European (non-Finnish) · 25/1,152,376 alleles
Filtering AF
0.00149%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00126%
Overall
0.00173%
27/1,556,668 alleles · very rare
exomes 21/1,405,104 · genomes 6/151,564 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00217% | 46,095 |
| Remaining individualsnot grpmax-eligible | 0.00166% | 60,404 |
| African / African-American | 0.00137% | 73,064 |
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.Pro174=
- Coding
- c.522C>G
- MANE Select
- NM_003221
- dbSNP
- rs886061565
- Type
- single nucleotide variant
- Location
- chr6:50823847 (GRCh38)
- Gene constraint
- LOEUF 0.353 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 65.95 · 1 PDB
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-pro174 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown