TFAP2A p.Pro40Ser
c.118C>T · rs1324911573 · VCV1407482
Computational evidence
| Protein change | ||
| AlphaMissense | 0.1297 | likely benign |
|---|---|---|
| REVEL | 0.347 | indeterminate |
| SaProt | LLR -6.40 | 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 9.6 | GERP 1.8, phastCons 1 |
| Regional constraint | o/e 0.88 | unconstrained · MANE · 10 kb · p 0.045 · regional, not allelic |
| Overall | ||
| CADD | 29.3 | 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 P38S vs ClinVar P40S) — verify the residue.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Ashkenazi Jewishnot grpmax-eligible | 0.0304% | 3,289 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,446 |
| European (non-Finnish)grpmax | 8.48e-05% | 1,179,866 |
Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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.Pro40Ser
- Coding
- c.118C>T
- MANE Select
- NM_001372066
- dbSNP
- rs1324911573
- Type
- single nucleotide variant
- Location
- chr6:10410269 (GRCh38)
- Gene constraint
- LOEUF 0.334 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 67.76 · 3 PDB
- Residue 38 UniProt numbering
- the 'disordered' region
Similar variants
- 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
- TFAP2A p.Ala342Pro Uncertain significance ★★ ⚠ same type
- TFAP2A p.Asn287Ser 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/tfap2a-p-pro40ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown