Is LDB3 p.Pro101= (c.303G>A) pathogenic?

LDB3 p.Pro101= (c.303G>A) is classified Likely benign in LDB3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-01). Ultra-rare (popmax 0.0198%, sas); Associated with Cardiovascular phenotype.

What condition is associated with LDB3 p.Pro101= (c.303G>A)?

LDB3 p.Pro101= (c.303G>A) is associated with Cardiovascular phenotype, myofibrillar myopathy 4 (ClinVar).

How common is LDB3 p.Pro101= (c.303G>A) in the general population?

LDB3 p.Pro101= (c.303G>A) is ultra-rare (popmax 0.0198%, sas) (gnomAD).

LDB3 p.Pro101=

c.303G>A · rs559350698 · VCV1149758

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0198%, sas)

Conditions

Cardiovascular phenotype

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 -3.7	GERP -4.1
Overall
CADD	3.13	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0198% South Asian · 18/91,082 alleles

Filtering AF 0.0127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.00266% 43/1,614,142 alleles · ultra-rare exomes 41/1,461,802 · genomes 2/152,340 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0198%	5,060
African / African-American	0.00932%	10,724
East Asian	0.00223%	44,874
Admixed American	0.00167%	60,026
Remaining individualsnot grpmax-eligible	0.0016%	62,508
European (non-Finnish)	0.00127%	78,665

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: LDB3
Protein: p.Pro101=
Coding: c.303G>A
MANE Select: NM_007078
dbSNP: rs559350698
Type: single nucleotide variant
Location: chr10:86680139 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.98 · 2 PDB
Residue 101: a UniProt-annotated variant site (in); the 'disordered' region

Full LDB3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: myofibrillar myopathy 4

Similar variants

LDB3 p.Pro101Leu Benign/Likely benign ★★ same residue
LDB3 p.Ala147Thr Pathogenic/Likely pathogenic ★★ same condition
LDB3 p.Ala165Val Pathogenic/Likely pathogenic ★★ same condition
LDB3 c.1231+4A>C Uncertain significance ★★ same condition
LDB3 c.1858-11C>A Uncertain significance ★★ same condition
LDB3 c.246-3C>T Uncertain significance ★★ same condition
LDB3 c.322-1G>A Uncertain significance ★★ same condition
LDB3 c.859+3G>A 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/ldb3-p-pro101 (accessed [today's date]).

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