Is LMOD3 p.Pro203Arg (c.608C>G) pathogenic?

LMOD3 p.Pro203Arg (c.608C>G) is classified Conflicting classifications of pathogenicity in LMOD3 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-26). AlphaMissense: likely benign (0.0791); Rare (popmax 0.162%, amr); Associated with nemaline myopathy 10.

What condition is associated with LMOD3 p.Pro203Arg (c.608C>G)?

LMOD3 p.Pro203Arg (c.608C>G) is associated with nemaline myopathy 10 (ClinVar).

How common is LMOD3 p.Pro203Arg (c.608C>G) in the general population?

LMOD3 p.Pro203Arg (c.608C>G) is rare (popmax 0.162%, amr) (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.Pro203Arg (c.608C>G)?

AlphaMissense predicts likely benign (score 0.0791) — an in-silico prediction, not a clinical call.

LMOD3 p.Pro203Arg

c.608C>G · rs775919681 · VCV475329

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0791 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.162%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

nemaline myopathy 10

Computational evidence

Protein change
AlphaMissense	0.0791	likely benign
REVEL	0.167	moderately benign-leaning
SaProt	LLR -5.67	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 1.8	GERP -2.5, phastCons 0.008
Regional constraint	o/e 1.11	unconstrained · MANE · 13 kb · p 0.0038 · regional, not allelic
Overall
CADD	5.863	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.162% Admixed American · 97/59,960 alleles

Filtering AF 0.136% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.126%

Overall 0.00607% 98/1,613,552 alleles · rare exomes 94/1,461,480 · genomes 4/152,072 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.162%	618
Remaining individualsnot grpmax-eligible	0.0016%	62,446

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.Pro203Arg
Coding: c.608C>G
MANE Select: NM_198271
dbSNP: rs775919681
Type: single nucleotide variant
Location: chr3:69119747 (GRCh38)
Gene constraint: LOEUF 0.948 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.79
Residue 203: 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-pro203arg (accessed [today's date]).

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