Is PEPD p.Ser460Arg (c.1380C>A) pathogenic?

PEPD p.Ser460Arg (c.1380C>A) is classified Uncertain significance in PEPD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-03). AlphaMissense: likely benign (0.2223); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PEPD p.Ser460Arg (c.1380C>A)?

PEPD p.Ser460Arg (c.1380C>A) is associated with Inborn genetic diseases (ClinVar).

How common is PEPD p.Ser460Arg (c.1380C>A) in the general population?

PEPD p.Ser460Arg (c.1380C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PEPD p.Ser460Arg (c.1380C>A)?

AlphaMissense predicts likely benign (score 0.2223) — an in-silico prediction, not a clinical call.

PEPD p.Ser460Arg

c.1380C>A · rs781482255 · VCV1918310

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2223 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2223	likely benign
REVEL	0.261	benign-leaning
SaProt	LLR -10.24	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.2	GERP -4.1
Regional constraint	o/e 1.00	unconstrained · MANE · 134 kb · p 0.97 · regional, not allelic
Overall
CADD	0.053	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PEPD
Protein: p.Ser460Arg
Coding: c.1380C>A
MANE Select: NM_000285
dbSNP: rs781482255
Type: single nucleotide variant
Location: chr19:33387446 (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 460: a β-strand

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PEPD p.Ala285Thr Uncertain significance ★★ ⚠ same condition
PEPD p.Arg196His Uncertain significance ★★ ⚠ same condition
PEPD p.Arg207His Uncertain significance ★★ ⚠ same condition
PEPD p.Arg233Gln Uncertain significance ★★ ⚠ same condition
PEPD p.Arg335His Uncertain significance ★★ ⚠ same condition
PEPD p.Arg388Cys Uncertain significance ★★ ⚠ same condition
PEPD p.Arg401Gln Uncertain significance ★★ ⚠ same condition
PEPD p.Arg431Ser Uncertain significance ★★ ⚠ 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-ser460arg (accessed [today's date]).

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