Is LMOD2 p.Arg437Ser (c.1311G>T) pathogenic?

LMOD2 p.Arg437Ser (c.1311G>T) is classified Uncertain significance in LMOD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-20). AlphaMissense: likely benign (0.1525); Very rare (popmax 8.79e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with LMOD2 p.Arg437Ser (c.1311G>T)?

LMOD2 p.Arg437Ser (c.1311G>T) is associated with Inborn genetic diseases (ClinVar).

How common is LMOD2 p.Arg437Ser (c.1311G>T) in the general population?

LMOD2 p.Arg437Ser (c.1311G>T) is very rare (popmax 8.79e-05%, nfe) (gnomAD).

What do computational predictors say about LMOD2 p.Arg437Ser (c.1311G>T)?

AlphaMissense predicts likely benign (score 0.1525) — an in-silico prediction, not a clinical call.

LMOD2 p.Arg437Ser

c.1311G>T · VCV3290993

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1525 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.79e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1525	likely benign
REVEL	0.012	strongly benign-leaning
SaProt	LLR -2.94	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 1	GERP 0.12, phastCons 0.18
Regional constraint	o/e 0.93	unconstrained · MANE · 7,778 bp · p 0.09 · regional, not allelic
Overall
CADD	4.451	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 8.79e-05% European (non-Finnish) · 1/1,137,430 alleles

Overall 0.000131% 2/1,529,258 alleles · very rare exomes 2/1,391,056 · genomes 0/138,202 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00167%	59,834
European (non-Finnish)grpmax	8.79e-05%	1,137,430

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: LMOD2
Protein: p.Arg437Ser
Coding: c.1311G>T
MANE Select: NM_207163
Type: single nucleotide variant
Location: chr7:123662897 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.14 · 6 PDB
Residue 437: 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-arg437ser (accessed [today's date]).

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