Is PDLIM3 p.Ser198= (c.594A>G) pathogenic?

PDLIM3 p.Ser198= (c.594A>G) is classified Likely benign in PDLIM3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-22). Very rare (popmax 0.00223%, eas); Associated with dilated cardiomyopathy.

What condition is associated with PDLIM3 p.Ser198= (c.594A>G)?

PDLIM3 p.Ser198= (c.594A>G) is associated with dilated cardiomyopathy, hypertrophic cardiomyopathy (ClinVar).

How common is PDLIM3 p.Ser198= (c.594A>G) in the general population?

PDLIM3 p.Ser198= (c.594A>G) is very rare (popmax 0.00223%, eas) (gnomAD).

PDLIM3 p.Ser198=

c.594A>G · rs200841741 · VCV1997875

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

dilated cardiomyopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP 0.33, phastCons 1
Overall
CADD	9.407	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,888 alleles

Overall 6.2e-05% 1/1,614,128 alleles · very rare exomes 0/1,461,790 · genomes 1/152,338 · 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: PDLIM3
Protein: p.Ser198=
Coding: c.594A>G
MANE Select: NM_014476
dbSNP: rs200841741
Type: single nucleotide variant
Location: chr4:185508367 (GRCh38)
Gene constraint: LOEUF 1.071 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.98

Full PDLIM3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

dilated cardiomyopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hypertrophic cardiomyopathy

Similar variants

PDLIM3 p.Ser198Leu Uncertain significance ★ ⚠ same residue
PDLIM3 p.Ala168Val Uncertain significance ★★ ⚠ same condition
PDLIM3 p.Ala171Thr Uncertain significance ★★ ⚠ same condition
PDLIM3 p.Ala304Gly Uncertain significance ★★ ⚠ same condition
PDLIM3 p.Ala308Thr Uncertain significance ★★ ⚠ same condition
PDLIM3 p.Ala308Val Uncertain significance ★★ ⚠ same condition
PDLIM3 p.Ala345Thr Uncertain significance ★★ ⚠ same condition
PDLIM3 p.Ala347Val 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/pdlim3-p-ser198 (accessed [today's date]).

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