Is PDLIM3 p.Pro277= (c.831G>A) pathogenic?

PDLIM3 p.Pro277= (c.831G>A) is classified Benign/Likely benign in PDLIM3 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-02). Low-frequency (popmax 3.21%, afr); Associated with hypertrophic cardiomyopathy.

What condition is associated with PDLIM3 p.Pro277= (c.831G>A)?

PDLIM3 p.Pro277= (c.831G>A) is associated with hypertrophic cardiomyopathy, dilated cardiomyopathy (ClinVar).

How common is PDLIM3 p.Pro277= (c.831G>A) in the general population?

PDLIM3 p.Pro277= (c.831G>A) is low-frequency (popmax 3.21%, afr) (gnomAD).

PDLIM3 p.Pro277=

c.831G>A · rs61734674 · VCV138672

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.21%, afr)

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 -5.1
Overall
CADD	0.073	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.21% African / African-American · 2,408/75,032 alleles

Filtering AF 3.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.06%

Overall 0.17% 2,745/1,614,100 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.21%	31
Remaining individualsnot grpmax-eligible	0.242%	414
Admixed American	0.203%	492
Middle Eastern	0.066%	1,516
South Asian	0.0143%	7,006
European (non-Finnish)	0.0039%	25,652
East Asian	0.00223%	44,878

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.Pro277=
Coding: c.831G>A
MANE Select: NM_014476
dbSNP: rs61734674
Type: single nucleotide variant
Location: chr4:185504549 (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.Pro277Leu 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-pro277 (accessed [today's date]).

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