Is LMOD2 p.Pro448Leu (c.1343C>T) pathogenic?

LMOD2 p.Pro448Leu (c.1343C>T) is classified Uncertain significance in LMOD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-22). AlphaMissense: likely benign (0.089); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with LMOD2 p.Pro448Leu (c.1343C>T)?

LMOD2 p.Pro448Leu (c.1343C>T) is associated with Inborn genetic diseases (ClinVar).

How common is LMOD2 p.Pro448Leu (c.1343C>T) in the general population?

LMOD2 p.Pro448Leu (c.1343C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LMOD2 p.Pro448Leu (c.1343C>T)?

AlphaMissense predicts likely benign (score 0.089) — an in-silico prediction, not a clinical call.

LMOD2 p.Pro448Leu

c.1343C>T · VCV4098729

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.089 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.089	likely benign
REVEL	0.085	moderately benign-leaning
SaProt	LLR -8.46	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 5.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 7,778 bp · p 0.09 · regional, not allelic
Overall
CADD	20.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: LMOD2
Protein: p.Pro448Leu
Coding: c.1343C>T
MANE Select: NM_207163
Type: single nucleotide variant
Location: chr7:123662929 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.14 · 6 PDB
Residue 448: a UniProt-annotated variant site (in cmd2g; no protein detected by western blot in cardiac tissue from a homozygous patient); the 'interaction with actin 2' region; the 'disordered' region

Full LMOD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LMOD2 p.Arg231Cys Uncertain significance ★★ ⚠ same condition
LMOD2 p.Glu276Lys Uncertain significance ★★ ⚠ same condition
LMOD2 p.Thr244Met Uncertain significance ★★ ⚠ same condition
LMOD2 p.Ala23Ser Uncertain significance ★ same condition
LMOD2 p.Ala23Val Uncertain significance ★ ⚠ same condition
LMOD2 p.Ala287Pro Uncertain significance ★ ⚠ same condition
LMOD2 p.Ala287Thr Uncertain significance ★ ⚠ same condition
LMOD2 p.Ala528Val 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/lmod2-p-pro448leu (accessed [today's date]).

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