Is PLPP5 p.Pro116Arg (c.347C>G) pathogenic?

PLPP5 p.Pro116Arg (c.347C>G) is classified Uncertain significance in PLPP5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-28). AlphaMissense: likely pathogenic (0.9754); Very rare (popmax 0.00223%, eas).

How common is PLPP5 p.Pro116Arg (c.347C>G) in the general population?

PLPP5 p.Pro116Arg (c.347C>G) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about PLPP5 p.Pro116Arg (c.347C>G)?

AlphaMissense predicts likely pathogenic (score 0.9754) — an in-silico prediction, not a clinical call.

PLPP5 p.Pro116Arg

c.347C>G · rs1208874048 · VCV2530644

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9754 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9754	likely pathogenic · top 8% in PLPP5
REVEL	0.97	strongly pathogenic-leaning
SaProt	LLR -15.79	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 9.8	GERP 1.5, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 4,752 bp · p 0.35 · regional, not allelic
Overall
CADD	29.7	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

Grpmax group 0.00223% East Asian · 1/44,878 alleles

Overall 6.2e-05% 1/1,613,270 alleles · very rare exomes 1/1,460,958 · genomes 0/152,312 · joint denominator

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: PLPP5
Protein: p.Pro116Arg
Coding: c.347C>G
MANE Select: NM_001102559
dbSNP: rs1208874048
Type: single nucleotide variant
Location: chr8:38267383 (GRCh38)
Gene constraint: LOEUF 1.825 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.84
Residue 116: the 'phosphatase sequence motif i' region

Full PLPP5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PLPP5 p.Ala156Pro Uncertain significance ★ ⚠ same type
PLPP5 p.Ala22Val Uncertain significance ★ ⚠ same type
PLPP5 p.Ala4Glu Uncertain significance ★ ⚠ same type
PLPP5 p.Ala5Val Uncertain significance ★ ⚠ same type
PLPP5 p.Ala96Pro Uncertain significance ★ ⚠ same type
PLPP5 p.Ala98Thr Uncertain significance ★ ⚠ same type
PLPP5 p.Arg115Gly Uncertain significance ★ ⚠ same type
PLPP5 p.Arg121Leu 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/plpp5-p-pro116arg (accessed [today's date]).

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