Is PEPD p.Val63Phe (c.187G>T) pathogenic?

PEPD p.Val63Phe (c.187G>T) is classified Uncertain significance in PEPD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-11). AlphaMissense: likely benign (0.1186); Very rare (popmax 0.00549%, sas); Associated with Inborn genetic diseases.

What condition is associated with PEPD p.Val63Phe (c.187G>T)?

PEPD p.Val63Phe (c.187G>T) is associated with Inborn genetic diseases (ClinVar).

How common is PEPD p.Val63Phe (c.187G>T) in the general population?

PEPD p.Val63Phe (c.187G>T) is very rare (popmax 0.00549%, sas) (gnomAD).

What do computational predictors say about PEPD p.Val63Phe (c.187G>T)?

AlphaMissense predicts likely benign (score 0.1186) — an in-silico prediction, not a clinical call.

PEPD p.Val63Phe

c.187G>T · rs778585918 · VCV1421876

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1186 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1186	likely benign
REVEL	0.181	moderately benign-leaning
SaProt	LLR -7.99	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.001	GERP -3.5, phastCons 0.001
Regional constraint	o/e 1.00	unconstrained · MANE · 134 kb · p 0.97 · regional, not allelic
Overall
CADD	4.661	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.00549% South Asian · 5/91,086 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.00211% 34/1,613,636 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,217
Admixed American	0.00333%	30,005
European (non-Finnish)	0.00229%	43,702

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.Val63Phe
Coding: c.187G>T
MANE Select: NM_000285
dbSNP: rs778585918
Type: single nucleotide variant
Location: chr19:33512607 (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 63: 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.Val63Ile Uncertain significance ★ ⚠ 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
PEPD p.Arg335His Uncertain significance ★★ ⚠ same condition
PEPD p.Arg388Cys Uncertain significance ★★ ⚠ same condition
PEPD p.Arg401Gln 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-val63phe (accessed [today's date]).

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