Is LMOD3 p.Ala43= (c.129C>T) pathogenic?

LMOD3 p.Ala43= (c.129C>T) is classified Likely benign in LMOD3 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-28). Rare (popmax 0.11%, nfe); Associated with nemaline myopathy 10.

What condition is associated with LMOD3 p.Ala43= (c.129C>T)?

LMOD3 p.Ala43= (c.129C>T) is associated with nemaline myopathy 10 (ClinVar).

How common is LMOD3 p.Ala43= (c.129C>T) in the general population?

LMOD3 p.Ala43= (c.129C>T) is rare (popmax 0.11%, nfe) (gnomAD).

How is Severe congenital nemaline myopathy inherited?

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

LMOD3 p.Ala43=

c.129C>T · rs201709177 · VCV475301

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.11%, nfe)

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 1.1	GERP -3.2, phastCons 1
Overall
CADD	8.704	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.11% European (non-Finnish) · 1,296/1,179,784 alleles

Filtering AF 0.105% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.103%

Overall 0.0851% 1,373/1,613,394 alleles · rare exomes 1,279/1,461,402 · genomes 94/151,992 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.11%	910
Remaining individualsnot grpmax-eligible	0.0512%	1,951
Admixed American	0.0367%	2,724
African / African-American	0.02%	4,990
South Asian	0.00549%	18,203
Finnishnot grpmax-eligible	0.00469%	21,319

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.Ala43=
Coding: c.129C>T
MANE Select: NM_198271
dbSNP: rs201709177
Type: single nucleotide variant
Location: chr3:69122258 (GRCh38)
Gene constraint: LOEUF 0.948 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.79
Residue 43: the 'interaction with tropomyosin alpha' 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.Ala43Thr 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-ala43 (accessed [today's date]).

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