Is PLPP5 p.His129Tyr (c.385C>T) pathogenic?

PLPP5 p.His129Tyr (c.385C>T) is classified Uncertain significance in PLPP5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-09). AlphaMissense: likely benign (0.1224); Absent from gnomAD v4.1.

How common is PLPP5 p.His129Tyr (c.385C>T) in the general population?

PLPP5 p.His129Tyr (c.385C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PLPP5 p.His129Tyr (c.385C>T)?

AlphaMissense predicts likely benign (score 0.1224) — an in-silico prediction, not a clinical call.

PLPP5 p.His129Tyr

c.385C>T · rs2487176872 · VCV3215394

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1224 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1224	likely benign
REVEL	0.215	benign-leaning
SaProt	LLR -10.16	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5.3	GERP -3.4, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 4,752 bp · p 0.35 · regional, not allelic
Overall
CADD	22.1	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: PLPP5
Protein: p.His129Tyr
Coding: c.385C>T
MANE Select: NM_015214 · reported on NM_001102559
dbSNP: rs2487176872
Type: single nucleotide variant
Location: chr8:38267345 (GRCh38)

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

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-his129tyr (accessed [today's date]).

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