Is PEPD p.Phe96Val (c.286T>G) pathogenic?

PEPD p.Phe96Val (c.286T>G) is classified Uncertain significance in PEPD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-29). AlphaMissense: likely pathogenic (0.7744); Absent from gnomAD v4.1.

How common is PEPD p.Phe96Val (c.286T>G) in the general population?

PEPD p.Phe96Val (c.286T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PEPD p.Phe96Val (c.286T>G)?

AlphaMissense predicts likely pathogenic (score 0.7744) — an in-silico prediction, not a clinical call.

PEPD p.Phe96Val

c.286T>G · rs2145353205 · VCV1347418

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7744 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7744	likely pathogenic
REVEL	0.97	strongly pathogenic-leaning
SaProt	LLR -12.68	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 11	GERP 2, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 134 kb · p 0.97 · regional, not allelic
Overall
CADD	28.0	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

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.Phe96Val
Coding: c.286T>G
MANE Select: NM_000285
dbSNP: rs2145353205
Type: single nucleotide variant
Location: chr19:33511071 (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 96: a β-strand

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

Similar variants

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
PEPD p.Arg265Ter 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-phe96val (accessed [today's date]).

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