TDP2 p.Pro348=
c.1044T>G · rs143596142 · VCV2656287
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.577%, mid)
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 -0.021 | GERP -3.8, phastCons 0.033 |
| Overall | ||
| CADD | 5.659 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.577%
Middle Eastern · 35/6,062 alleles
Filtering AF
0.427%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.375%
Overall
0.0874%
1,411/1,614,136 alleles · rare
exomes 1,263/1,461,792 · genomes 148/152,344 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.577% | 173 |
| Ashkenazi Jewishnot grpmax-eligible | 0.27% | 370 |
| African / African-American | 0.18% | 556 |
| Remaining individualsnot grpmax-eligible | 0.138% | 727 |
| Admixed American | 0.132% | 760 |
| European (non-Finnish) | 0.0779% | 1,284 |
| South Asian | 0.0571% | 1,752 |
| Finnishnot grpmax-eligible | 0.039% | 2,561 |
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
- TDP2
- Protein
- p.Pro348=
- Coding
- c.1044T>G
- MANE Select
- NM_016614
- dbSNP
- rs143596142
- Type
- single nucleotide variant
- Location
- chr6:24650833 (GRCh38)
- Gene constraint
- LOEUF 1.197 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.61 · 5 PDB
Similar variants
- TDP2 p.Arg134Ter Pathogenic ★★ same type
- TDP2 p.Asn167= Likely benign ★★ same type
- TDP2 p.Asn59Asp Likely benign ★★ same type
- TDP2 p.Asn89Ser Benign/Likely benign ★★ same type
- TDP2 p.Leu28Val Benign/Likely benign ★★ same type
- TDP2 p.Ser60= Likely benign ★★ same type
- TDP2 p.Arg317Ter Pathogenic ★ same type
- TDP2 p.Ser130Ter 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/tdp2-p-pro348 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown