Is LDB3 p.Phe695= (c.2085C>T) pathogenic?

LDB3 p.Phe695= (c.2085C>T) is classified Uncertain significance in LDB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-26). Very rare (popmax 0.00223%, eas); Associated with myofibrillar myopathy 4.

What condition is associated with LDB3 p.Phe695= (c.2085C>T)?

LDB3 p.Phe695= (c.2085C>T) is associated with myofibrillar myopathy 4 (ClinVar).

How common is LDB3 p.Phe695= (c.2085C>T) in the general population?

LDB3 p.Phe695= (c.2085C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

LDB3 p.Phe695=

Q: How is Late-onset distal myopathy, Markesbery-Griggs type inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.2085C>T · rs1335300730 · VCV2895400

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

myofibrillar myopathy 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.32	donor loss · deltas
Constraint at this position
Conservation	phyloP 6	GERP 1.4, phastCons 1
Overall
CADD	12.92	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,898 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.000992% 16/1,613,632 alleles · very rare exomes 13/1,461,430 · genomes 3/152,202 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,898
European (non-Finnish)	0.00127%	78,646

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.Phe695=
Coding: c.2085C>T
MANE Select: NM_007078
dbSNP: rs1335300730
Type: single nucleotide variant
Location: chr10:86726243 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.98 · 2 PDB
Residue 695: a UniProt-annotated variant site (in cmd2l; likely pathogenic); the lim zinc-binding 3 domain

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

Disease context

myofibrillar myopathy 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Late-onset distal myopathy, Markesbery-Griggs type (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult
Prevalence: <1 / 1 000 000 (Worldwide)

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-phe695 (accessed [today's date]).

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