Is LDB3 p.Ser2Tyr (c.5C>A) pathogenic?

LDB3 p.Ser2Tyr (c.5C>A) is classified Uncertain significance in LDB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-06-29). AlphaMissense: ambiguous (0.5277); Very rare (popmax 8.48e-05%, nfe); Associated with cardiomyopathy.

What condition is associated with LDB3 p.Ser2Tyr (c.5C>A)?

LDB3 p.Ser2Tyr (c.5C>A) is associated with cardiomyopathy (ClinVar).

How common is LDB3 p.Ser2Tyr (c.5C>A) in the general population?

LDB3 p.Ser2Tyr (c.5C>A) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about LDB3 p.Ser2Tyr (c.5C>A)?

AlphaMissense predicts ambiguous (score 0.5277) — an in-silico prediction, not a clinical call.

LDB3 p.Ser2Tyr

c.5C>A · rs1564626030 · VCV626702

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5277 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

cardiomyopathy

Computational evidence

Protein change
AlphaMissense	0.5277	ambiguous
REVEL	0.352	indeterminate
SaProt	LLR -11.88	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 64 kb · p 0.14 · regional, not allelic
Overall
CADD	27.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,842 alleles

Overall 6.2e-05% 1/1,613,256 alleles · very rare exomes 1/1,460,984 · genomes 0/152,272 · joint denominator

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.Ser2Tyr
Coding: c.5C>A
MANE Select: NM_007078
dbSNP: rs1564626030
Type: single nucleotide variant
Location: chr10:86668696 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.98 · 2 PDB
Residue 2: the pdz domain; a β-strand

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

Disease context

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

Similar variants

LDB3 p.Ser2Pro Uncertain significance ★ ⚠ same residue
LDB3 p.Ser2Thr Uncertain significance ★ ⚠ same residue
LDB3 p.Ala147Thr Pathogenic/Likely pathogenic ★★ same condition
LDB3 p.Ala165Val Pathogenic/Likely pathogenic ★★ same condition
LDB3 p.Ala389Thr Uncertain significance ★★ ⚠ same condition
LDB3 p.Ala501Val Uncertain significance ★★ ⚠ same condition
LDB3 p.Arg404Gln Uncertain significance ★★ ⚠ same condition
LDB3 p.Arg559Gln 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-ser2tyr (accessed [today's date]).

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