Is LMOD2 p.Arg413His (c.1238G>A) pathogenic?

LMOD2 p.Arg413His (c.1238G>A) is classified Likely benign in LMOD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-15). AlphaMissense: likely benign (0.0891); Ultra-rare (popmax 0.0558%, eas).

How common is LMOD2 p.Arg413His (c.1238G>A) in the general population?

LMOD2 p.Arg413His (c.1238G>A) is ultra-rare (popmax 0.0558%, eas) (gnomAD).

What do computational predictors say about LMOD2 p.Arg413His (c.1238G>A)?

AlphaMissense predicts likely benign (score 0.0891) — an in-silico prediction, not a clinical call.

LMOD2 p.Arg413His

c.1238G>A · VCV4897658

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0891 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0558%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0891	likely benign
REVEL	0.025	moderately benign-leaning
SaProt	LLR -7.24	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 3.9	GERP -0.93, phastCons 0.98
Regional constraint	o/e 0.93	unconstrained · MANE · 7,778 bp · p 0.09 · regional, not allelic
Overall
CADD	10.92	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 0.0558% East Asian · 25/44,806 alleles

Filtering AF 0.0387% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0331%

Overall 0.00794% 128/1,612,314 alleles · ultra-rare exomes 116/1,460,926 · genomes 12/151,388 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0558%	1,792
Middle Eastern	0.0343%	2,919
South Asian	0.0187%	5,350
African / African-American	0.00803%	12,454
European (non-Finnish)	0.00636%	15,726
Remaining individualsnot grpmax-eligible	0.0032%	31,215
Admixed American	0.00167%	59,856

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.Arg413His
Coding: c.1238G>A
MANE Select: NM_207163
Type: single nucleotide variant
Location: chr7:123662824 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.14 · 6 PDB
Residue 413: 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

Similar variants

LMOD2 p.Arg231Cys Uncertain significance ★★ ⚠ same type
LMOD2 p.Glu276Lys Uncertain significance ★★ ⚠ same type
LMOD2 p.Thr244Met Uncertain significance ★★ ⚠ same type
LMOD2 c.1617+220A>G Benign ★★ same type
LMOD2 c.273+30C>A Benign ★★ same type
LMOD2 c.-54C>T Benign ★★ same type
LMOD2 p.Glu100= Benign ★★ same type
LMOD2 p.Ile221Thr Likely benign ★★ ⚠ same type

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-arg413his (accessed [today's date]).

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