PEPD p.Ala252=
c.756C>T · rs374710449 · VCV1533931
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0496%, 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 -12 | GERP -3.3 |
| Overall | ||
| CADD | 0.089 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0496%
Middle Eastern · 3/6,054 alleles
Filtering AF
0.0134%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00719%
Overall
0.00684%
110/1,607,618 alleles · ultra-rare
exomes 96/1,455,272 · genomes 14/152,346 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0496% | 2,018 |
| Admixed American | 0.015% | 6,661 |
| Remaining individualsnot grpmax-eligible | 0.00963% | 10,383 |
| European (non-Finnish) | 0.00715% | 13,983 |
| Finnishnot grpmax-eligible | 0.00628% | 15,925 |
| African / African-American | 0.004% | 24,974 |
| South Asian | 0.0011% | 90,860 |
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.Ala252=
- Coding
- c.756C>T
- MANE Select
- NM_000285
- dbSNP
- rs374710449
- Type
- single nucleotide variant
- Location
- chr19:33411734 (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 252
- an α-helix
Similar variants
- 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
- PEPD p.Arg265Ter 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-ala252 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown