Is PDLIM3 p.Ser18= (c.54A>G) pathogenic?

PDLIM3 p.Ser18= (c.54A>G) is classified Likely benign in PDLIM3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-14). Ultra-rare (popmax 0.0172%, nfe); Associated with hypertrophic cardiomyopathy.

What condition is associated with PDLIM3 p.Ser18= (c.54A>G)?

PDLIM3 p.Ser18= (c.54A>G) is associated with hypertrophic cardiomyopathy, dilated cardiomyopathy (ClinVar).

How common is PDLIM3 p.Ser18= (c.54A>G) in the general population?

PDLIM3 p.Ser18= (c.54A>G) is ultra-rare (popmax 0.0172%, nfe) (gnomAD).

PDLIM3 p.Ser18=

c.54A>G · rs768654855 · VCV454479

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0172%, nfe)

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 -20	GERP -5.2
Overall
CADD	0.587	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0172% European (non-Finnish) · 203/1,177,546 alleles

Filtering AF 0.0152% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0145%

Overall 0.0132% 213/1,608,108 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0172%	5,801
Remaining individualsnot grpmax-eligible	0.00965%	10,367
African / African-American	0.00404%	24,727
Admixed American	0.00168%	59,546

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.Ser18=
Coding: c.54A>G
MANE Select: NM_014476
dbSNP: rs768654855
Type: single nucleotide variant
Location: chr4:185535381 (GRCh38)
Gene constraint: LOEUF 1.071 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.98
Residue 18: the pdz domain; a modified residue (phosphoserine)

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.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
PDLIM3 p.Ala38Val 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-ser18 (accessed [today's date]).

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