Is LDB3 p.Ser320fs (c.948_957dup) pathogenic?

LDB3 p.Ser320fs (c.948957dup) is classified Conflicting classifications of pathogenicity in LDB3 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-03-25). Very rare (popmax 0.00534%, afr); Associated with Cardiovascular phenotype.

What condition is associated with LDB3 p.Ser320fs (c.948_957dup)?

LDB3 p.Ser320fs (c.948_957dup) is associated with Cardiovascular phenotype, myofibrillar myopathy 4 (ClinVar).

How common is LDB3 p.Ser320fs (c.948_957dup) in the general population?

LDB3 p.Ser320fs (c.948_957dup) is very rare (popmax 0.00534%, afr) (gnomAD).

LDB3 p.Ser320fs

c.948_957dup · rs760482922 · VCV1767097

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 8 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.9	GERP 1.2, phastCons 1
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,932 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00031% 5/1,613,082 alleles · very rare exomes 3/1,460,872 · genomes 2/152,210 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,733
European (non-Finnish)	8.47e-05%	1,179,993

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.Ser320fs
Coding: c.948_957dup
MANE Select: NM_007078
dbSNP: rs760482922
Type: Duplication
Location: chr10:86706575 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.98 · 2 PDB
Residue 320: 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.Ser320= Uncertain significance ★ same residue
LDB3 p.Ser349_Thr350dup Uncertain significance ★★ same condition
LDB3 p.Thr8_Gly9insLeuThr Uncertain significance ★★ same condition
LDB3 c.1232-12dup Benign/Likely benign ★★ same condition
LDB3 p.Ala482fs Pathogenic ★ same condition
LDB3 p.Asp359fs Pathogenic ★ same condition
LDB3 p.Gln191fs Pathogenic ★ same condition
LDB3 p.Gln97fs Pathogenic ★ 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-ser320fs (accessed [today's date]).

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