Is LMOD2 p.Ala23Ser (c.67G>T) pathogenic?

LMOD2 p.Ala23Ser (c.67G>T) is classified Uncertain significance in LMOD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-08). AlphaMissense: ambiguous (0.5526); Very rare (popmax 0.00222%, sas); Associated with Inborn genetic diseases.

What condition is associated with LMOD2 p.Ala23Ser (c.67G>T)?

LMOD2 p.Ala23Ser (c.67G>T) is associated with Inborn genetic diseases (ClinVar).

How common is LMOD2 p.Ala23Ser (c.67G>T) in the general population?

LMOD2 p.Ala23Ser (c.67G>T) is very rare (popmax 0.00222%, sas) (gnomAD).

What do computational predictors say about LMOD2 p.Ala23Ser (c.67G>T)?

AlphaMissense predicts ambiguous (score 0.5526) — an in-silico prediction, not a clinical call.

LMOD2 p.Ala23Ser

c.67G>T · VCV3290992

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5526 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00222%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5526	ambiguous
REVEL	0.302	indeterminate
SaProt	LLR -8.40	tolerated
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 1.3, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 7,778 bp · p 0.09 · regional, not allelic
Overall
CADD	26.5	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 0.00222% South Asian · 2/90,068 alleles

Filtering AF 0.000369% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000138%

Overall 0.000248% 4/1,610,230 alleles · very rare exomes 3/1,458,012 · genomes 1/152,218 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00222%	45,034
Remaining individualsnot grpmax-eligible	0.0016%	62,370
European (non-Finnish)	8.49e-05%	1,178,387

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.Ala23Ser
Coding: c.67G>T
MANE Select: NM_207163
Type: single nucleotide variant
Location: chr7:123656030 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.14 · 6 PDB
Residue 23: the 'interaction with actin 1' region; the 'interaction with tropomyosin alpha' region; a turn

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.Ala23Val Uncertain significance ★ ⚠ same residue
LMOD2 p.Ala23Thr 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.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-ala23ser (accessed [today's date]).

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