PRDM13 p.Pro474=
c.1422G>A · rs377013141 · VCV1478523
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0148%, afr)
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 -1 | GERP -2.5 |
| Overall | ||
| CADD | 4.458 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0148%
African / African-American · 11/74,574 alleles
Filtering AF
0.00819%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00636%
Overall
0.000747%
12/1,607,042 alleles · ultra-rare
exomes 6/1,454,834 · genomes 6/152,208 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0148% | 6,779 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,182 |
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
- PRDM13
- Protein
- p.Pro474=
- Coding
- c.1422G>A
- MANE Select
- NM_021620
- dbSNP
- rs377013141
- Type
- single nucleotide variant
- Location
- chr6:99614057 (GRCh38)
- Gene constraint
- LOEUF 0.694 · pLI 0.08 (gnomAD)
- Structure
- AlphaFold pLDDT 53.52
Similar variants
- PRDM13 p.Pro474Leu Uncertain significance ★ ⚠ same residue
- PRDM13 c.277-10T>G Uncertain significance ★★ same type
- PRDM13 p.Ala231Val Uncertain significance ★★ ⚠ same type
- PRDM13 p.Ala258Val Uncertain significance ★★ ⚠ same type
- PRDM13 p.Ala298Pro Uncertain significance ★★ ⚠ same type
- PRDM13 p.Ala414Glu Uncertain significance ★★ ⚠ same type
- PRDM13 p.Ala510Thr Uncertain significance ★★ ⚠ same type
- PRDM13 p.Ala566Thr 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/prdm13-p-pro474 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown