Is PEPD p.Asp378= (c.1134C>T) pathogenic?

PEPD p.Asp378= (c.1134C>T) is classified Conflicting classifications of pathogenicity in PEPD (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-15). Rare (popmax 0.314%, mid); Associated with prolidase deficiency.

What condition is associated with PEPD p.Asp378= (c.1134C>T)?

PEPD p.Asp378= (c.1134C>T) is associated with prolidase deficiency (ClinVar).

How common is PEPD p.Asp378= (c.1134C>T) in the general population?

PEPD p.Asp378= (c.1134C>T) is rare (popmax 0.314%, mid) (gnomAD).

How is Prolidase deficiency inherited?

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

PEPD p.Asp378=

c.1134C>T · rs761553925 · VCV892557

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.314%, mid)

Conditions

prolidase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.49 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.46	GERP -4.3, phastCons 0.002
Overall
CADD	9.848	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.314% Middle Eastern · 19/6,060 alleles

Filtering AF 0.205% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.171%

Overall 0.0146% 235/1,611,600 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.314%	319
South Asian	0.202%	496
Remaining individualsnot grpmax-eligible	0.024%	4,163
African / African-American	0.008%	12,503
Admixed American	0.00668%	14,962
Finnishnot grpmax-eligible	0.00159%	62,862
European (non-Finnish)	0.000594%	168,482

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.Asp378=
Coding: c.1134C>T
MANE Select: NM_000285
dbSNP: rs761553925
Type: single nucleotide variant
Location: chr19:33391313 (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-asp378 (accessed [today's date]).

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