Is LMOD3 p.Ser47fs (c.138dup) pathogenic?

LMOD3 p.Ser47fs (c.138dup) is classified Pathogenic in LMOD3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-04-17). Ultra-rare (popmax 0.0165%, mid); Associated with nemaline myopathy 10.

What condition is associated with LMOD3 p.Ser47fs (c.138dup)?

LMOD3 p.Ser47fs (c.138dup) is associated with nemaline myopathy 10 (ClinVar).

How common is LMOD3 p.Ser47fs (c.138dup) in the general population?

LMOD3 p.Ser47fs (c.138dup) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

How is Severe congenital nemaline myopathy inherited?

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

LMOD3 p.Ser47fs

c.138dup · rs727502797 · VCV162215

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

nemaline myopathy 10

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 3
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1	GERP -0.74, phastCons 0.78

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000434% 7/1,613,744 alleles · ultra-rare exomes 7/1,461,460 · genomes 0/152,284 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
European (non-Finnish)	0.000509%	196,636

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.Ser47fs
Coding: c.138dup
MANE Select: NM_198271
dbSNP: rs727502797
Type: Duplication
Location: chr3:69122248 (GRCh38)
Gene constraint: LOEUF 0.948 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.79
Residue 47: the 'interaction with tropomyosin alpha' region; 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.Ile213fs Pathogenic ★★ same condition
LMOD3 p.Arg492fs Pathogenic ★ same condition
LMOD3 p.Asp295fs Pathogenic ★ same condition
LMOD3 p.Ter561LeuextTer? Uncertain significance ★ same condition
LMOD3 p.Asn367fs Pathogenic/Likely pathogenic ★★ same condition
LMOD3 p.Asp242fs Pathogenic/Likely pathogenic ★★ same condition
LMOD3 p.Gln36Ter Pathogenic ★★ same condition
LMOD3 p.Leu550Phe Pathogenic ★★ ⚠ 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-ser47fs (accessed [today's date]).

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