Is PDLIM3 p.Gly331= (c.993C>A) pathogenic?

PDLIM3 p.Gly331= (c.993C>A) is classified Benign/Likely benign in PDLIM3 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-01). Rare (popmax 0.406%, afr); Associated with dilated cardiomyopathy.

What condition is associated with PDLIM3 p.Gly331= (c.993C>A)?

PDLIM3 p.Gly331= (c.993C>A) is associated with dilated cardiomyopathy, hypertrophic cardiomyopathy (ClinVar).

How common is PDLIM3 p.Gly331= (c.993C>A) in the general population?

PDLIM3 p.Gly331= (c.993C>A) is rare (popmax 0.406%, afr) (gnomAD).

PDLIM3 p.Gly331=

c.993C>A · rs139493914 · VCV227013

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.406%, afr)

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 3.9	GERP 1.8, phastCons 1
Overall
CADD	10.83	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.406% African / African-American · 305/75,044 alleles

Filtering AF 0.369% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.354%

Overall 0.0408% 659/1,614,196 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.406%	246
Remaining individualsnot grpmax-eligible	0.118%	845
Admixed American	0.1%	1,000
Middle Eastern	0.0825%	1,212
European (non-Finnish)	0.0182%	5,489

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.Gly331=
Coding: c.993C>A
MANE Select: NM_014476
dbSNP: rs139493914
Type: single nucleotide variant
Location: chr4:185502396 (GRCh38)
Gene constraint: LOEUF 1.071 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.98
Residue 331: the lim zinc-binding domain

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.Gly331Val 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-gly331 (accessed [today's date]).

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