Is LDB3 p.Pro26Ser (c.76C>T) pathogenic?

LDB3 p.Pro26Ser (c.76C>T) is classified Conflicting classifications of pathogenicity in LDB3 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2023-01-25). AlphaMissense: likely pathogenic (0.9879); Very rare (popmax 0.0011%, sas); Associated with LDB3-related disorder.

What condition is associated with LDB3 p.Pro26Ser (c.76C>T)?

LDB3 p.Pro26Ser (c.76C>T) is associated with LDB3-related disorder, myofibrillar myopathy 4 (ClinVar).

How common is LDB3 p.Pro26Ser (c.76C>T) in the general population?

LDB3 p.Pro26Ser (c.76C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about LDB3 p.Pro26Ser (c.76C>T)?

AlphaMissense predicts likely pathogenic (score 0.9879) — an in-silico prediction, not a clinical call.

LDB3 p.Pro26Ser

c.76C>T · rs778865072 · VCV1305257

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9879 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

LDB3-related disorder

Computational evidence

Protein change
AlphaMissense	0.9879	likely pathogenic
REVEL	0.478	indeterminate
SaProt	LLR -12.83	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
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 0.0011% South Asian · 1/91,078 alleles

Overall 6.2e-05% 1/1,613,066 alleles · very rare exomes 1/1,460,736 · genomes 0/152,330 · 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.Pro26Ser
Coding: c.76C>T
MANE Select: NM_007078
dbSNP: rs778865072
Type: single nucleotide variant
Location: chr10:86668767 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.98 · 2 PDB
Residue 26: the pdz domain; a β-strand

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

Disease context

LDB3-related disorder

Also linked: myofibrillar myopathy 4

Similar variants

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
LDB3 c.859+5G>C 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-pro26ser (accessed [today's date]).

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