Is LMOD3 p.Pro522= (c.1566G>A) pathogenic?

LMOD3 p.Pro522= (c.1566G>A) is classified Likely benign in LMOD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-04). Ultra-rare (popmax 0.0826%, eas); Associated with nemaline myopathy 10.

What condition is associated with LMOD3 p.Pro522= (c.1566G>A)?

LMOD3 p.Pro522= (c.1566G>A) is associated with nemaline myopathy 10 (ClinVar).

How common is LMOD3 p.Pro522= (c.1566G>A) in the general population?

LMOD3 p.Pro522= (c.1566G>A) is ultra-rare (popmax 0.0826%, eas) (gnomAD).

How is Severe congenital nemaline myopathy inherited?

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

LMOD3 p.Pro522=

c.1566G>A · rs765741615 · VCV2139400

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0826%, eas)

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 -7.6	GERP -5.2
Overall
CADD	3.411	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0826% East Asian · 37/44,786 alleles

Filtering AF 0.0616% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0543%

Overall 0.00248% 40/1,611,302 alleles · ultra-rare exomes 39/1,461,640 · genomes 1/149,662 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0826%	1,210
African / African-American	0.0027%	37,051
Admixed American	0.00168%	59,598

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.Pro522=
Coding: c.1566G>A
MANE Select: NM_198271
dbSNP: rs765741615
Type: single nucleotide variant
Location: chr3:69118789 (GRCh38)
Gene constraint: LOEUF 0.948 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.79
Residue 522: 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.Pro522Leu 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-pro522 (accessed [today's date]).

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