Is PEPD p.Arg431Ser (c.1291C>A) pathogenic?

PEPD p.Arg431Ser (c.1291C>A) is classified Uncertain significance in PEPD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-20). AlphaMissense: ambiguous (0.4008); No allele count reported in gnomAD v4.1 (AN 1,597,770); Associated with Inborn genetic diseases.

What condition is associated with PEPD p.Arg431Ser (c.1291C>A)?

PEPD p.Arg431Ser (c.1291C>A) is associated with Inborn genetic diseases (ClinVar).

How common is PEPD p.Arg431Ser (c.1291C>A) in the general population?

PEPD p.Arg431Ser (c.1291C>A) is no allele count reported in gnomAD v4.1 (AN 1,597,770) (gnomAD).

What do computational predictors say about PEPD p.Arg431Ser (c.1291C>A)?

AlphaMissense predicts ambiguous (score 0.4008) — an in-silico prediction, not a clinical call.

PEPD p.Arg431Ser

c.1291C>A · rs751121493 · VCV1933985

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4008 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,597,770)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4008	ambiguous
REVEL	0.281	benign-leaning
SaProt	LLR -8.68	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.8	GERP 0.7, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 134 kb · p 0.97 · regional, not allelic
Overall
CADD	21.3	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

No allele count reported in gnomAD v4.1 (AN 1,597,770). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PEPD
Protein: p.Arg431Ser
Coding: c.1291C>A
MANE Select: NM_000285
dbSNP: rs751121493
Type: single nucleotide variant
Location: chr19:33387943 (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 431: an α-helix

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.Arg431Cys Uncertain significance ★★ ⚠ same residue
PEPD p.Arg431His Uncertain significance ★★ ⚠ same residue
PEPD p.Arg431Pro Uncertain significance ★ ⚠ same residue
PEPD p.Arg431= Likely benign ★ same residue
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

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-arg431ser (accessed [today's date]).

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