Is LMOD2 p.Arg44His (c.131G>A) pathogenic?

LMOD2 p.Arg44His (c.131G>A) is classified Likely benign in LMOD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-22). AlphaMissense: likely benign (0.0691); Very rare (popmax 0.00503%, amr); Associated with Inborn genetic diseases.

What condition is associated with LMOD2 p.Arg44His (c.131G>A)?

LMOD2 p.Arg44His (c.131G>A) is associated with Inborn genetic diseases (ClinVar).

How common is LMOD2 p.Arg44His (c.131G>A) in the general population?

LMOD2 p.Arg44His (c.131G>A) is very rare (popmax 0.00503%, amr) (gnomAD).

What do computational predictors say about LMOD2 p.Arg44His (c.131G>A)?

AlphaMissense predicts likely benign (score 0.0691) — an in-silico prediction, not a clinical call.

LMOD2 p.Arg44His

c.131G>A · rs754535632 · VCV3119391

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0691 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00503%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0691	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -5.31	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 0.32	GERP -0.81, phastCons 0.001
Regional constraint	o/e 0.93	unconstrained · MANE · 7,778 bp · p 0.09 · regional, not allelic
Overall
CADD	17.13	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 0.00503% Admixed American · 3/59,648 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000901%

Overall 0.00199% 32/1,611,254 alleles · very rare exomes 30/1,459,132 · genomes 2/152,122 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00802%	12,474
Admixed Americangrpmax	0.00503%	19,883
South Asian	0.00443%	22,590
European (non-Finnish)	0.0017%	58,942

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.Arg44His
Coding: c.131G>A
MANE Select: NM_207163
dbSNP: rs754535632
Type: single nucleotide variant
Location: chr7:123656094 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.14 · 6 PDB
Residue 44: the 'interaction with actin 1' region; the 'interaction with tropomyosin alpha' 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.Arg44Cys Uncertain significance ★ ⚠ same residue
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

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-arg44his (accessed [today's date]).

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