Is LMOD3 p.Pro382Ser (c.1144C>T) pathogenic?

LMOD3 p.Pro382Ser (c.1144C>T) is classified Benign in LMOD3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-22). AlphaMissense: likely pathogenic (0.9327); Low-frequency (popmax 2.5%, afr); Associated with nemaline myopathy 10.

What condition is associated with LMOD3 p.Pro382Ser (c.1144C>T)?

LMOD3 p.Pro382Ser (c.1144C>T) is associated with nemaline myopathy 10 (ClinVar).

How common is LMOD3 p.Pro382Ser (c.1144C>T) in the general population?

LMOD3 p.Pro382Ser (c.1144C>T) is low-frequency (popmax 2.5%, afr) (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.Pro382Ser (c.1144C>T)?

AlphaMissense predicts likely pathogenic (score 0.9327) — an in-silico prediction, not a clinical call.

LMOD3 p.Pro382Ser

c.1144C>T · rs74350755 · VCV475296

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9327 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.5%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

nemaline myopathy 10

Computational evidence

Protein change
AlphaMissense	0.9327	likely pathogenic · top 9% in LMOD3
REVEL	0.75	pathogenic-leaning
SaProt	LLR -12.69	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 2.8, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 13 kb · p 0.0038 · regional, not allelic
Overall
CADD	25.8	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 2.5% African / African-American · 1,874/74,972 alleles

Filtering AF 2.41% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.37%

Overall 0.137% 2,215/1,613,864 alleles · low-frequency exomes 1,069/1,461,696 · genomes 1,146/152,168 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.5%	40
Admixed American	0.295%	339
Remaining individualsnot grpmax-eligible	0.219%	456
Middle Eastern	0.0495%	2,021
European (non-Finnish)	0.00195%	51,299
South Asian	0.0011%	91,066

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.Pro382Ser
Coding: c.1144C>T
MANE Select: NM_198271
dbSNP: rs74350755
Type: single nucleotide variant
Location: chr3:69119211 (GRCh38)
Gene constraint: LOEUF 0.948 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.79

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-pro382ser (accessed [today's date]).

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