Is LMOD3 p.Val487Met (c.1459G>A) pathogenic?

LMOD3 p.Val487Met (c.1459G>A) is classified Uncertain significance in LMOD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-22). AlphaMissense: likely benign (0.118); Very rare (popmax 0.00135%, afr).

How common is LMOD3 p.Val487Met (c.1459G>A) in the general population?

LMOD3 p.Val487Met (c.1459G>A) is very rare (popmax 0.00135%, afr) (gnomAD).

What do computational predictors say about LMOD3 p.Val487Met (c.1459G>A)?

AlphaMissense predicts likely benign (score 0.118) — an in-silico prediction, not a clinical call.

LMOD3 p.Val487Met

c.1459G>A · VCV4527150

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.118 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00135%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.118	likely benign
REVEL	0.051	moderately benign-leaning
SaProt	LLR -7.09	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 1.8	GERP 0.61, phastCons 0.068
Regional constraint	o/e 1.11	unconstrained · MANE · 13 kb · p 0.0038 · regional, not allelic
Overall
CADD	18.83	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 0.00135% African / African-American · 1/74,170 alleles

Overall 0.000124% 2/1,611,702 alleles · very rare exomes 2/1,461,636 · genomes 0/150,066 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00135%	74,170
European (non-Finnish)	8.48e-05%	1,179,485

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: LMOD3
Protein: p.Val487Met
Coding: c.1459G>A
MANE Select: NM_198271
Type: single nucleotide variant
Location: chr3:69118896 (GRCh38)
Gene constraint: LOEUF 0.948 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.79

Full LMOD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

LMOD3 p.Val487Ala Uncertain significance ★★ ⚠ same residue
LMOD3 p.Gln36Ter Pathogenic ★★ same type
LMOD3 p.Leu550Phe Pathogenic ★★ ⚠ same type
LMOD3 p.Ala299Thr Uncertain significance ★★ ⚠ same type
LMOD3 p.Ala475Thr Uncertain significance ★★ ⚠ same type
LMOD3 p.Ala502Gly Uncertain significance ★★ ⚠ same type
LMOD3 p.Ala548Thr Uncertain significance ★★ ⚠ same type
LMOD3 p.Arg111Cys Uncertain significance ★★ ⚠ 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/lmod3-p-val487met (accessed [today's date]).

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