Is PEPD p.Ser490= (c.1470T>C) pathogenic?

PEPD p.Ser490= (c.1470T>C) is classified Benign/Likely benign in PEPD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-21). Rare (popmax 0.294%, sas); Associated with prolidase deficiency.

What condition is associated with PEPD p.Ser490= (c.1470T>C)?

PEPD p.Ser490= (c.1470T>C) is associated with prolidase deficiency (ClinVar).

How common is PEPD p.Ser490= (c.1470T>C) in the general population?

PEPD p.Ser490= (c.1470T>C) is rare (popmax 0.294%, sas) (gnomAD).

How is Prolidase deficiency inherited?

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

PEPD p.Ser490=

c.1470T>C · rs529823817 · VCV328783

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.294%, sas)

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 0.56	GERP -2.8, phastCons 0.019
Overall
CADD	3.471	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.294% South Asian · 268/91,080 alleles

Filtering AF 0.265% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.254%

Overall 0.018% 291/1,614,004 alleles · rare exomes 274/1,461,652 · genomes 17/152,352 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.294%	340
Remaining individualsnot grpmax-eligible	0.0352%	2,841
European (non-Finnish)	8.47e-05%	1,180,043

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.Ser490=
Coding: c.1470T>C
MANE Select: NM_000285
dbSNP: rs529823817
Type: single nucleotide variant
Location: chr19:33387356 (GRCh38)
Gene constraint: LOEUF 1.132 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 97.62 · 21 PDB

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-ser490 (accessed [today's date]).

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