Is PLN p.Thr8Pro (c.22A>C) pathogenic?

PLN p.Thr8Pro (c.22A>C) is classified Conflicting classifications of pathogenicity in PLN (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2017-06-14). AlphaMissense: ambiguous (0.3796); Absent from gnomAD v4.1; Associated with PLN-related disorders.

What condition is associated with PLN p.Thr8Pro (c.22A>C)?

PLN p.Thr8Pro (c.22A>C) is associated with PLN-related disorders, dilated cardiomyopathy 1P (ClinVar).

How common is PLN p.Thr8Pro (c.22A>C) in the general population?

PLN p.Thr8Pro (c.22A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PLN p.Thr8Pro (c.22A>C)?

AlphaMissense predicts ambiguous (score 0.3796) — an in-silico prediction, not a clinical call.

PLN p.Thr8Pro

c.22A>C · rs1060502977 · VCV410617

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3796 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

PLN-related disorders

Computational evidence

Protein change
AlphaMissense	0.3796	ambiguous
REVEL	0.959	strongly pathogenic-leaning
SaProt	LLR -14.08	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 155 bp · p 0.64 · regional, not allelic
Overall
CADD	25.6	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: PLN
Protein: p.Thr8Pro
Coding: c.22A>C
MANE Select: NM_001042475 · reported on NM_002667
dbSNP: rs1060502977
Type: single nucleotide variant
Location: chr6:118558943 (GRCh38)

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

Disease context

PLN-related disorders

Also linked: dilated cardiomyopathy 1P

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/pln-p-thr8pro (accessed [today's date]).

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