Is LMOD2 p.Val273Ile (c.817G>A) pathogenic?

LMOD2 p.Val273Ile (c.817G>A) is classified Likely benign in LMOD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-11). AlphaMissense: likely benign (0.0568); Very rare (popmax 0.00439%, sas); Associated with Inborn genetic diseases.

What condition is associated with LMOD2 p.Val273Ile (c.817G>A)?

LMOD2 p.Val273Ile (c.817G>A) is associated with Inborn genetic diseases (ClinVar).

How common is LMOD2 p.Val273Ile (c.817G>A) in the general population?

LMOD2 p.Val273Ile (c.817G>A) is very rare (popmax 0.00439%, sas) (gnomAD).

What do computational predictors say about LMOD2 p.Val273Ile (c.817G>A)?

AlphaMissense predicts likely benign (score 0.0568) — an in-silico prediction, not a clinical call.

LMOD2 p.Val273Ile

c.817G>A · VCV4047829

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0568 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0568	likely benign
REVEL	0.175	moderately benign-leaning
SaProt	LLR -5.16	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 -2	GERP -4.3
Regional constraint	o/e 0.93	unconstrained · MANE · 7,778 bp · p 0.09 · regional, not allelic
Overall
CADD	0.358	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 0.00439% South Asian · 4/91,090 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.00031% 5/1,613,844 alleles · very rare exomes 4/1,461,706 · genomes 1/152,138 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,773
Remaining individualsnot grpmax-eligible	0.0016%	62,466

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.Val273Ile
Coding: c.817G>A
MANE Select: NM_207163
Type: single nucleotide variant
Location: chr7:123662403 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.14 · 6 PDB
Residue 273: a β-strand; the 'interaction with actin 2' 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-val273ile (accessed [today's date]).

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