Is PEPD p.Ser286= (c.858C>T) pathogenic?

PEPD p.Ser286= (c.858C>T) is classified Likely benign in PEPD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-26). Ultra-rare (popmax 0.0293%, nfe); Associated with prolidase deficiency.

What condition is associated with PEPD p.Ser286= (c.858C>T)?

PEPD p.Ser286= (c.858C>T) is associated with prolidase deficiency (ClinVar).

How common is PEPD p.Ser286= (c.858C>T) in the general population?

PEPD p.Ser286= (c.858C>T) is ultra-rare (popmax 0.0293%, nfe) (gnomAD).

How is Prolidase deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

PEPD p.Ser286=

c.858C>T · rs375354020 · VCV1460757

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0293%, nfe)

Conditions

prolidase deficiency

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 -3.5
Overall
CADD	0.871	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0293% European (non-Finnish) · 346/1,179,916 alleles

Filtering AF 0.0267% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0257%

Overall 0.0232% 375/1,613,080 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0293%	3,410
Remaining individualsnot grpmax-eligible	0.0288%	3,471
African / African-American	0.012%	8,325
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,600
South Asian	0.0011%	91,058

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.Ser286=
Coding: c.858C>T
MANE Select: NM_000285
dbSNP: rs375354020
Type: single nucleotide variant
Location: chr19:33401830 (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 286: a β-strand

Full PEPD gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

prolidase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Prolidase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood, Infancy, Neonatal

Similar variants

PEPD c.442-1G>C Pathogenic/Likely pathogenic ★★ same condition
PEPD c.504-1G>A Pathogenic/Likely pathogenic ★★ same condition
PEPD c.549-1G>A Pathogenic ★★ same condition
PEPD c.819-1G>A Likely pathogenic ★★ same condition
PEPD p.Ala212Pro Pathogenic/Likely pathogenic ★★ same condition
PEPD p.Arg184Ter Pathogenic ★★ same condition
PEPD p.Arg265Ter Pathogenic ★★ same condition
PEPD p.Asp276Asn Pathogenic/Likely pathogenic ★★ same condition

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-ser286 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown