Is PDLIM3 p.Arg241= (c.721C>A) pathogenic?

PDLIM3 p.Arg241= (c.721C>A) is classified Likely benign in PDLIM3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-16). No allele count reported in gnomAD v4.1 (AN 1,611,994); Associated with hypertrophic cardiomyopathy.

What condition is associated with PDLIM3 p.Arg241= (c.721C>A)?

PDLIM3 p.Arg241= (c.721C>A) is associated with hypertrophic cardiomyopathy, dilated cardiomyopathy (ClinVar).

How common is PDLIM3 p.Arg241= (c.721C>A) in the general population?

PDLIM3 p.Arg241= (c.721C>A) is no allele count reported in gnomAD v4.1 (AN 1,611,994) (gnomAD).

PDLIM3 p.Arg241=

c.721C>A · rs768909650 · VCV1757753

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,611,994)

Conditions

hypertrophic 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 3.5	GERP 1.8, phastCons 0.57
Overall
CADD	13.91	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,611,994). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PDLIM3
Protein: p.Arg241=
Coding: c.721C>A
MANE Select: NM_014476
dbSNP: rs768909650
Type: single nucleotide variant
Location: chr4:185506594 (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

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

Also linked: dilated cardiomyopathy

Similar variants

PDLIM3 p.Arg241Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
PDLIM3 p.Arg241Leu Uncertain significance ★ ⚠ same residue
PDLIM3 p.Arg241Trp 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

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-arg241 (accessed [today's date]).

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