PRDM6 p.Pro425=
c.1275G>A · VCV3355494
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.37%, sas)
Conditions
1
PRDM6-related disorder
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 -7.5 | GERP -4 |
| Overall | ||
| CADD | 0.263 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.37%
South Asian · 311/84,048 alleles
Filtering AF
0.336%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.323%
Overall
0.0256%
397/1,552,152 alleles · rare
exomes 376/1,399,970 · genomes 21/152,182 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.37% | 270 |
| Remaining individualsnot grpmax-eligible | 0.0879% | 1,137 |
| East Asian | 0.0415% | 2,407 |
| African / African-American | 0.00821% | 12,187 |
| Admixed American | 0.00784% | 12,750 |
| European (non-Finnish) | 0.000523% | 191,181 |
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
- PRDM6
- Protein
- p.Pro425=
- Coding
- c.1275G>A
- MANE Select
- NM_001136239
- Type
- single nucleotide variant
- Location
- chr5:123170887 (GRCh38)
- Gene constraint
- LOEUF 0.649 · pLI 0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 57.72
Disease context
PRDM6-related disorder
Similar variants
- PRDM6 p.Pro425Leu Uncertain significance ★ ⚠ same residue
- PRDM6 p.Ala291Thr Benign same condition
- PRDM6 p.Ala41= Benign same condition
- PRDM6 p.Arg561= Likely benign same condition
- PRDM6 p.Leu105= Likely benign same condition
- PRDM6 p.Leu44= Benign same condition
- PRDM6 p.Pro59_Glu60insPro Benign same condition
- PRDM6 p.Leu26Phe 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/prdm6-p-pro425 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown