PEPD p.Phe75=
c.225C>T · rs538934934 · VCV1934365
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0187%, afr)
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 -4.1 | GERP -3.9 |
| Overall | ||
| CADD | 3.222 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0187%
African / African-American · 14/75,018 alleles
Filtering AF
0.0112%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00903%
Overall
0.00291%
47/1,613,942 alleles · ultra-rare
exomes 37/1,461,674 · genomes 10/152,268 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0187% | 5,358 |
| Admixed American | 0.01% | 10,003 |
| South Asian | 0.00988% | 10,118 |
| East Asian | 0.00223% | 44,884 |
| European (non-Finnish) | 0.00144% | 69,404 |
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
- PEPD
- Protein
- p.Phe75=
- Coding
- c.225C>T
- MANE Select
- NM_000285
- dbSNP
- rs538934934
- Type
- single nucleotide variant
- Location
- chr19:33511132 (GRCh38)
- Gene constraint
- LOEUF 1.132 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 97.62 · 21 PDB
- Residue 75
- an α-helix
Similar variants
- PEPD p.Phe75Leu Uncertain significance ★ ⚠ same residue
- PEPD c.442-1G>C Pathogenic/Likely pathogenic ★★ same type
- PEPD c.504-1G>A Pathogenic/Likely pathogenic ★★ same type
- PEPD c.549-1G>A Pathogenic ★★ same type
- PEPD c.818+2T>G Likely pathogenic ★★ same type
- PEPD c.819-1G>A Likely pathogenic ★★ same type
- PEPD p.Ala212Pro Pathogenic/Likely pathogenic ★★ same type
- PEPD p.Arg184Ter 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/pepd-p-phe75 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown