TCF3 p.Arg558=
c.1674C>T · rs568282400 · VCV1911699
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0535%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.76 | GERP -3.5, phastCons 1 |
| Overall | ||
| CADD | 18.95 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0535%
East Asian · 24/44,892 alleles
Filtering AF
0.0368%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0313%
Overall
0.00359%
58/1,613,936 alleles · ultra-rare
exomes 43/1,461,584 · genomes 15/152,352 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0535% | 1,871 |
| African / African-American | 0.0173% | 5,773 |
| Middle Eastern | 0.0165% | 6,060 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,621 |
| South Asian | 0.00329% | 30,363 |
| Admixed American | 0.00167% | 60,024 |
| European (non-Finnish) | 0.00102% | 98,325 |
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
- TCF3
- Protein
- p.Arg558=
- Coding
- c.1674C>T
- MANE Select
- NM_003200 · reported on NM_001136139
- dbSNP
- rs568282400
- Type
- single nucleotide variant
- Location
- chr19:1612346 (GRCh38)
- Gene constraint
- LOEUF 1.239 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 52.42 · 5 PDB
- Residue 558
- the bhlh domain; a UniProt-annotated variant site (in agm8b; decreased protein abundance)
Similar variants
- TCF3 p.Arg558His Uncertain significance ★ same residue
- TCF3 p.Arg321Ter Pathogenic ★★ same type
- TCF3 p.Glu555Lys Pathogenic ★★ same type
- TCF3 c.1327-3C>A Uncertain significance ★★ same type
- TCF3 c.652+5A>G Uncertain significance ★★ same type
- TCF3 c.955+3A>G Uncertain significance ★★ same type
- TCF3 c.955+6G>A Uncertain significance ★★ same type
- TCF3 p.Ala109Ser 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/tcf3-p-arg558 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown