PRDM13 p.Val458=
c.1374C>A · rs377263054 · VCV726858
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.16%, 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 0.99 | GERP 0.66, phastCons 0.97 |
| Overall | ||
| CADD | 9.698 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.16%
African / African-American · 119/74,604 alleles
Filtering AF
0.136%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.127%
Overall
0.00845%
136/1,610,066 alleles · rare
exomes 65/1,457,724 · genomes 71/152,342 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.16% | 627 |
| Admixed American | 0.0167% | 5,981 |
| Middle Eastern | 0.0165% | 6,044 |
| Remaining individualsnot grpmax-eligible | 0.00963% | 10,389 |
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.Val458=
- Coding
- c.1374C>A
- MANE Select
- NM_021620
- dbSNP
- rs377263054
- Type
- single nucleotide variant
- Location
- chr6:99614009 (GRCh38)
- Gene constraint
- LOEUF 0.694 · pLI 0.08 (gnomAD)
- Structure
- AlphaFold pLDDT 53.52
Similar variants
- 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
- PRDM13 p.Ala5Ser 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-val458 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown