Is LMOD3 p.Pro49= (c.147C>T) pathogenic?

LMOD3 p.Pro49= (c.147C>T) is classified Likely benign in LMOD3 (ClinVar, Single submitter, 2 submitters; last evaluated 2026-02-01). Ultra-rare (popmax 0.0684%, amr); Associated with nemaline myopathy 10.

What condition is associated with LMOD3 p.Pro49= (c.147C>T)?

LMOD3 p.Pro49= (c.147C>T) is associated with nemaline myopathy 10 (ClinVar).

How common is LMOD3 p.Pro49= (c.147C>T) in the general population?

LMOD3 p.Pro49= (c.147C>T) is ultra-rare (popmax 0.0684%, amr) (gnomAD).

How is Severe congenital nemaline myopathy inherited?

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

LMOD3 p.Pro49=

c.147C>T · rs184423475 · VCV542092

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0684%, amr)

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 -5.4	GERP -5.2
Overall
CADD	2.796	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0684% Admixed American · 41/59,960 alleles

Filtering AF 0.0518% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0459%

Overall 0.00614% 99/1,613,494 alleles · ultra-rare exomes 66/1,461,348 · genomes 33/152,146 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0684%	1,462
Remaining individualsnot grpmax-eligible	0.0256%	3,904
African / African-American	0.00534%	18,744
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,598
European (non-Finnish)	0.00314%	31,885

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.Pro49=
Coding: c.147C>T
MANE Select: NM_198271
dbSNP: rs184423475
Type: single nucleotide variant
Location: chr3:69122240 (GRCh38)
Gene constraint: LOEUF 0.948 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.79
Residue 49: 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.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
LMOD3 p.Arg111His 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-pro49 (accessed [today's date]).

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