Is LIMS2 p.Ile147= (c.441C>A) pathogenic?

LIMS2 p.Ile147= (c.441C>A) is classified Benign in LIMS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-17). Rare (popmax 0.429%, eas); Associated with autosomal recessive limb-girdle muscular dystrophy type 2W.

What condition is associated with LIMS2 p.Ile147= (c.441C>A)?

LIMS2 p.Ile147= (c.441C>A) is associated with autosomal recessive limb-girdle muscular dystrophy type 2W (ClinVar).

How common is LIMS2 p.Ile147= (c.441C>A) in the general population?

LIMS2 p.Ile147= (c.441C>A) is rare (popmax 0.429%, eas) (gnomAD).

LIMS2 p.Ile147=

c.441C>A · rs199563092 · VCV704868

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.429%, eas)

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2W

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -5.6	GERP -3.8
Overall
CADD	0.546	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.429% East Asian · 184/42,884 alleles

Filtering AF 0.378% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.359%

Overall 0.014% 221/1,576,556 alleles · rare exomes 191/1,424,192 · genomes 30/152,364 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.429%	233
Remaining individualsnot grpmax-eligible	0.0311%	3,217
South Asian	0.0151%	6,616
European (non-Finnish)	0.000431%	232,239

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: LIMS2
Protein: p.Ile147=
Coding: c.441C>A
MANE Select: NM_001161403
dbSNP: rs199563092
Type: single nucleotide variant
Location: chr2:127642991 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.16 · 1 PDB
Residue 147: the lim zinc-binding 3 domain

Full LIMS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive limb-girdle muscular dystrophy type 2W — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GPR17 p.Tyr147= Likely benign ★ same residue
LIMS2 c.11+1287G>T Uncertain significance ★★ same condition
LIMS2 c.11+1305G>A Uncertain significance ★★ same condition
LIMS2 c.12-6769C>G Uncertain significance ★★ same condition
LIMS2 c.754-2A>G Uncertain significance ★★ same condition
LIMS2 p.Ala110Val Uncertain significance ★★ ⚠ same condition
LIMS2 p.Ala212Val Uncertain significance ★★ ⚠ same condition
LIMS2 p.Ala25Thr 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/lims2-p-ile147 (accessed [today's date]).

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