Is LMOD3 p.Leu511= (c.1533C>T) pathogenic?

LMOD3 p.Leu511= (c.1533C>T) is classified Likely benign in LMOD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-12). Very rare (popmax 0.00541%, afr); Associated with nemaline myopathy 10.

What condition is associated with LMOD3 p.Leu511= (c.1533C>T)?

LMOD3 p.Leu511= (c.1533C>T) is associated with nemaline myopathy 10 (ClinVar).

How common is LMOD3 p.Leu511= (c.1533C>T) in the general population?

LMOD3 p.Leu511= (c.1533C>T) is very rare (popmax 0.00541%, afr) (gnomAD).

How is Severe congenital nemaline myopathy inherited?

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

LMOD3 p.Leu511=

c.1533C>T · rs999543342 · VCV2805996

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00541%, afr)

Conditions

nemaline myopathy 10

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.4	GERP 1.7, phastCons 1
Overall
CADD	7.022	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00541% African / African-American · 4/73,880 alleles

Filtering AF 0.00176% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00105%

Overall 0.000248% 4/1,610,930 alleles · very rare exomes 1/1,461,634 · genomes 3/149,296 · 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: LMOD3
Protein: p.Leu511=
Coding: c.1533C>T
MANE Select: NM_198271
dbSNP: rs999543342
Type: single nucleotide variant
Location: chr3:69118822 (GRCh38)
Gene constraint: LOEUF 0.948 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.79
Residue 511: the 'disordered' region

Full LMOD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

nemaline myopathy 10 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Severe congenital nemaline myopathy (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

LMOD3 p.Leu511His Uncertain significance ★ ⚠ same residue
LMOD3 p.Gln36Ter Pathogenic ★★ same condition
LMOD3 p.Leu550Phe Pathogenic ★★ ⚠ same condition
LMOD3 p.Ala299Thr Uncertain significance ★★ ⚠ same condition
LMOD3 p.Ala475Thr Uncertain significance ★★ ⚠ same condition
LMOD3 p.Ala502Gly Uncertain significance ★★ ⚠ same condition
LMOD3 p.Ala548Thr Uncertain significance ★★ ⚠ same condition
LMOD3 p.Arg111Cys 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/lmod3-p-leu511 (accessed [today's date]).

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