Is LDB3 p.Val55Ile (c.163G>A) pathogenic?

LDB3 p.Val55Ile (c.163G>A) is classified Benign/Likely benign in LDB3 (ClinVar, Multiple submitters, 16 submitters; last evaluated 2026-01-27). AlphaMissense: likely benign (0.0607); Common (popmax 5.94%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Cardiovascular phenotype.

What condition is associated with LDB3 p.Val55Ile (c.163G>A)?

LDB3 p.Val55Ile (c.163G>A) is associated with Cardiovascular phenotype, cardiomyopathy, dilated cardiomyopathy 1C (ClinVar).

What do computational predictors say about LDB3 p.Val55Ile (c.163G>A)?

AlphaMissense predicts likely benign (score 0.0607) — an in-silico prediction, not a clinical call.

LDB3 p.Val55Ile

Q: How common is LDB3 p.Val55Ile (c.163G>A) in the general population?

LDB3 p.Val55Ile (c.163G>A) is common (popmax 5.94%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.163G>A · rs3740343 · VCV45530

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 16 submitters

AlphaMissense

likely benign

0.0607 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 5.94%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0607	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -7.89	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP -5.1, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 64 kb · p 0.14 · regional, not allelic
Overall
CADD	21.9	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 5.94% East Asian · 2,667/44,888 alleles

Filtering AF 5.75% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.68%

Overall 0.233% 3,762/1,614,106 alleles · common exomes 3,179/1,461,842 · genomes 583/152,264 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	5.94%	17
Ashkenazi Jewishnot grpmax-eligible	0.534%	187
Admixed American	0.517%	194
Remaining individualsnot grpmax-eligible	0.482%	208
South Asian	0.165%	607
African / African-American	0.068%	1,471
Middle Eastern	0.033%	3,031
European (non-Finnish)	0.0104%	9,594

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.Val55Ile
Coding: c.163G>A
MANE Select: NM_007078
dbSNP: rs3740343
Type: single nucleotide variant
Location: chr10:86679436 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.98 · 2 PDB
Residue 55: the pdz domain; a UniProt-annotated variant site (in)

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: cardiomyopathy dilated cardiomyopathy 1C myofibrillar myopathy 4

Similar variants

LDB3 p.Val55Ala Uncertain significance ★ ⚠ 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-val55ile (accessed [today's date]).

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