Is PEPD p.Arg237Ser (c.709C>A) pathogenic?

PEPD p.Arg237Ser (c.709C>A) is classified Uncertain significance in PEPD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-10). AlphaMissense: likely pathogenic (0.9964); No allele count reported in gnomAD v4.1 (AN 1,586,824).

How common is PEPD p.Arg237Ser (c.709C>A) in the general population?

PEPD p.Arg237Ser (c.709C>A) is no allele count reported in gnomAD v4.1 (AN 1,586,824) (gnomAD).

What do computational predictors say about PEPD p.Arg237Ser (c.709C>A)?

AlphaMissense predicts likely pathogenic (score 0.9964) — an in-silico prediction, not a clinical call.

PEPD p.Arg237Ser

c.709C>A · rs766107449 · VCV2108474

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9964 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,586,824)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9964	likely pathogenic · top 1% in PEPD
REVEL	0.734	pathogenic-leaning
SaProt	LLR -13.47	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.8, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 134 kb · p 0.97 · regional, not allelic
Overall
CADD	29.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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 1,586,824). 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.Arg237Ser
Coding: c.709C>A
MANE Select: NM_000285
dbSNP: rs766107449
Type: single nucleotide variant
Location: chr19:33413606 (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

Similar variants

PEPD p.Arg237His Uncertain significance ★★ ⚠ same residue
PEPD c.442-1G>C Pathogenic/Likely pathogenic ★★ same type
PEPD c.504-1G>A Pathogenic/Likely pathogenic ★★ same type
PEPD c.549-1G>A Pathogenic ★★ same type
PEPD c.818+2T>G Likely pathogenic ★★ same type
PEPD c.819-1G>A Likely pathogenic ★★ same type
PEPD p.Ala212Pro Pathogenic/Likely pathogenic ★★ same type
PEPD p.Arg184Ter Pathogenic ★★ same type

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-arg237ser (accessed [today's date]).

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