Is PEPD p.Glu131= (c.393G>A) pathogenic?

PEPD p.Glu131= (c.393G>A) is classified Uncertain significance in PEPD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-03-11). Very rare (popmax 0.00334%, amr); Associated with prolidase deficiency.

What condition is associated with PEPD p.Glu131= (c.393G>A)?

PEPD p.Glu131= (c.393G>A) is associated with prolidase deficiency (ClinVar).

How common is PEPD p.Glu131= (c.393G>A) in the general population?

PEPD p.Glu131= (c.393G>A) is very rare (popmax 0.00334%, amr) (gnomAD).

How is Prolidase deficiency inherited?

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

PEPD p.Glu131=

c.393G>A · rs771409768 · VCV891671

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Conditions

prolidase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.63	donor loss · deltas
Pangolin	Δ0.59	loss · gain 0.42 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.72	GERP -0.48, phastCons 1
Overall
CADD	19.26	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00334% Admixed American · 2/59,968 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000316% 5/1,581,910 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00488%	20,482
Admixed Americangrpmax	0.00334%	29,984

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Glu131=
Coding: c.393G>A
MANE Select: NM_000285
dbSNP: rs771409768
Type: single nucleotide variant
Location: chr19:33500938 (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 131: an α-helix

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 p.Glu131Asp Uncertain significance ★ ⚠ same residue
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

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-glu131 (accessed [today's date]).

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