Is PLPBP p.Ser84Pro (c.250T>C) pathogenic?

PLPBP p.Ser84Pro (c.250T>C) is classified Uncertain significance in PLPBP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-16). AlphaMissense: likely benign (0.3174); Absent from gnomAD v4.1.

How common is PLPBP p.Ser84Pro (c.250T>C) in the general population?

PLPBP p.Ser84Pro (c.250T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PLPBP p.Ser84Pro (c.250T>C)?

AlphaMissense predicts likely benign (score 0.3174) — an in-silico prediction, not a clinical call.

PLPBP p.Ser84Pro

c.250T>C · rs2487371787 · VCV2134257

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3174 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3174	likely benign
REVEL	0.127	moderately benign-leaning
SaProt	LLR -12.23	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 5	GERP 2.4, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 12 kb · p 9.5e-06 · regional, not allelic
Overall
CADD	22.7	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: PLPBP
Protein: p.Ser84Pro
Coding: c.250T>C
MANE Select: NM_007198
dbSNP: rs2487371787
Type: single nucleotide variant
Location: chr8:37766286 (GRCh38)
Gene constraint: LOEUF 1.049 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.49
Residue 84: a UniProt-annotated variant site (in epeo1); a UniProt-annotated variant site (in epeo1; decreased expression at the mrna level; undetectable at the protein level in patient's fibroblasts)

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

Similar variants

PLPBP p.Ser84fs Pathogenic ★★ same residue
PLPBP c.207+1G>T Pathogenic/Likely pathogenic ★★ same type
PLPBP c.320-2A>G Pathogenic ★★ same type
PLPBP p.Arg241Gln Pathogenic/Likely pathogenic ★★ same type
PLPBP p.Pro87Leu Pathogenic/Likely pathogenic ★★ ⚠ same type
PLPBP p.Ala232= Uncertain significance ★★ same type
PLPBP p.Arg205Trp Uncertain significance ★★ ⚠ same type
PLPBP p.Arg250Gln Uncertain significance ★★ ⚠ 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/plpbp-p-ser84pro (accessed [today's date]).

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