Is LMOD3 p.Ser134Pro (c.400T>C) pathogenic?

LMOD3 p.Ser134Pro (c.400T>C) is classified Uncertain significance in LMOD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-10). AlphaMissense: likely benign (0.0694); Very rare (popmax 8.63e-05%, nfe); Associated with nemaline myopathy 10.

What condition is associated with LMOD3 p.Ser134Pro (c.400T>C)?

LMOD3 p.Ser134Pro (c.400T>C) is associated with nemaline myopathy 10 (ClinVar).

How common is LMOD3 p.Ser134Pro (c.400T>C) in the general population?

LMOD3 p.Ser134Pro (c.400T>C) is very rare (popmax 8.63e-05%, nfe) (gnomAD).

How is Severe congenital nemaline myopathy inherited?

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

What do computational predictors say about LMOD3 p.Ser134Pro (c.400T>C)?

AlphaMissense predicts likely benign (score 0.0694) — an in-silico prediction, not a clinical call.

LMOD3 p.Ser134Pro

c.400T>C · rs1283065889 · VCV959540

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0694 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.63e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

nemaline myopathy 10

Computational evidence

Protein change
AlphaMissense	0.0694	likely benign
REVEL	0.166	moderately benign-leaning
SaProt	LLR -8.94	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.72	GERP -2.8, phastCons 0.005
Regional constraint	o/e 1.11	unconstrained · MANE · 13 kb · p 0.0038 · regional, not allelic
Overall
CADD	3.805	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.63e-05% European (non-Finnish) · 1/1,159,406 alleles

Overall 6.34e-05% 1/1,576,372 alleles · very rare exomes 1/1,425,096 · genomes 0/151,276 · 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.Ser134Pro
Coding: c.400T>C
MANE Select: NM_198271
dbSNP: rs1283065889
Type: single nucleotide variant
Location: chr3:69119955 (GRCh38)
Gene constraint: LOEUF 0.948 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.79
Residue 134: 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.Ser134Ala 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-ser134pro (accessed [today's date]).

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