TCF20 p.Pro560=
c.1680G>A · rs745974078 · VCV3017630
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00988%, sas)
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 -6.4 | GERP -4.6 |
| Overall | ||
| CADD | 2.9 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00988%
South Asian · 9/91,088 alleles
Filtering AF
0.00514%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00375%
Overall
0.00186%
30/1,613,940 alleles · very rare
exomes 27/1,461,796 · genomes 3/152,144 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00988% | 10,121 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,827 |
| African / African-American | 0.00267% | 37,448 |
| Admixed American | 0.00167% | 59,998 |
| European (non-Finnish) | 0.00127% | 78,670 |
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
- TCF20
- Protein
- p.Pro560=
- Coding
- c.1680G>A
- MANE Select
- NM_001378418
- dbSNP
- rs745974078
- Type
- single nucleotide variant
- Location
- chr22:42213626 (GRCh38)
- Gene constraint
- LOEUF 0.05 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 39.03
- Residue 560
- a UniProt-annotated variant site (in ddviba); the 'disordered' region
Similar variants
- TCF20 p.Pro560Leu Uncertain significance ★ ⚠ same residue
- TCF20 p.Arg1907Ter Pathogenic ★★ same type
- TCF20 p.Arg742Ter Pathogenic ★★ same type
- TCF20 p.Gln1082Ter Pathogenic/Likely pathogenic ★★ same type
- TCF20 p.Gln471Ter Pathogenic ★★ same type
- TCF20 p.Gln754Ter Pathogenic ★★ same type
- TCF20 p.Gln935Ter Pathogenic ★★ same type
- TCF20 p.Trp1861Ter Pathogenic/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/tcf20-p-pro560 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown