Is LMOD3 p.Pro450= (c.1350G>A) pathogenic?

LMOD3 p.Pro450= (c.1350G>A) is classified Likely benign in LMOD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-10). Very rare (popmax 0.0022%, sas); Associated with nemaline myopathy 10.

What condition is associated with LMOD3 p.Pro450= (c.1350G>A)?

LMOD3 p.Pro450= (c.1350G>A) is associated with nemaline myopathy 10 (ClinVar).

How common is LMOD3 p.Pro450= (c.1350G>A) in the general population?

LMOD3 p.Pro450= (c.1350G>A) is very rare (popmax 0.0022%, sas) (gnomAD).

How is Severe congenital nemaline myopathy inherited?

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

LMOD3 p.Pro450=

c.1350G>A · rs748774777 · VCV1077622

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

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 -1.5	GERP -4.8
Overall
CADD	0.955	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,038 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.00062% 10/1,613,532 alleles · very rare exomes 10/1,461,654 · genomes 0/151,878 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,519
European (non-Finnish)	0.000678%	147,473

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.Pro450=
Coding: c.1350G>A
MANE Select: NM_198271
dbSNP: rs748774777
Type: single nucleotide variant
Location: chr3:69119005 (GRCh38)
Gene constraint: LOEUF 0.948 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.79
Residue 450: 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.Pro450Ser Uncertain significance ★★ ⚠ same residue
LMOD3 p.Pro450Ala Uncertain significance ★ ⚠ same residue
LMOD3 p.Pro450Leu 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

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-pro450 (accessed [today's date]).

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