TFAP2A p.Pro99=
c.297C>G · rs758008816 · VCV3020843
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00644%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.681 | pathogenic-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.079 | GERP -0.047, phastCons 0.008 |
| Overall | ||
| CADD | 11.46 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00644%
European (non-Finnish) · 76/1,179,844 alleles
Filtering AF
0.00528%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00482%
Overall
0.0049%
79/1,612,846 alleles · very rare
exomes 76/1,460,804 · genomes 3/152,042 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00644% | 15,524 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,452 |
| Finnishnot grpmax-eligible | 0.00158% | 63,220 |
| African / African-American | 0.00134% | 74,866 |
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.Pro99=
- Coding
- c.297C>G
- MANE Select
- NM_001372066
- dbSNP
- rs758008816
- Type
- single nucleotide variant
- Location
- chr6:10410090 (GRCh38)
- Gene constraint
- LOEUF 0.334 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 67.76 · 3 PDB
- Residue 99
- the 'disordered' region
Similar variants
- TFAP2A p.Pro99Leu Uncertain significance ★ ⚠ same residue
- TFAP2A p.Pro99Ser Uncertain significance ★ ⚠ same residue
- TFAP2A p.Ala258Val Pathogenic/Likely pathogenic ★★ same type
- TFAP2A p.Arg239Gln Pathogenic/Likely pathogenic ★★ same type
- TFAP2A p.Arg325Ter Pathogenic ★★ same type
- TFAP2A p.Gln32Ter Likely pathogenic ★★ same type
- TFAP2A p.Glu235Lys Likely pathogenic ★★ same type
- TFAP2A p.His386Tyr Likely pathogenic ★★ 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/tfap2a-p-pro99 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown