Is LIMS2 p.Ser156= (c.468C>T) pathogenic?

LIMS2 p.Ser156= (c.468C>T) is classified Likely benign in LIMS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-26). Ultra-rare (popmax 0.015%, amr); Associated with autosomal recessive limb-girdle muscular dystrophy type 2W.

What condition is associated with LIMS2 p.Ser156= (c.468C>T)?

LIMS2 p.Ser156= (c.468C>T) is associated with autosomal recessive limb-girdle muscular dystrophy type 2W (ClinVar).

How common is LIMS2 p.Ser156= (c.468C>T) in the general population?

LIMS2 p.Ser156= (c.468C>T) is ultra-rare (popmax 0.015%, amr) (gnomAD).

LIMS2 p.Ser156=

c.468C>T · rs772862811 · VCV767257

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, amr)

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.9	GERP -3.8
Overall
CADD	4.32	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.015% Admixed American · 8/53,308 alleles

Filtering AF 0.00743% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00544%

Overall 0.00127% 20/1,569,290 alleles · ultra-rare exomes 14/1,417,064 · genomes 6/152,226 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.015%	6,664
Ashkenazi Jewishnot grpmax-eligible	0.00347%	28,836
Remaining individualsnot grpmax-eligible	0.00164%	60,818
African / African-American	0.00135%	73,842
South Asian	0.00117%	85,406
European (non-Finnish)	0.000691%	144,665

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.Ser156=
Coding: c.468C>T
MANE Select: NM_001161403
dbSNP: rs772862811
Type: single nucleotide variant
Location: chr2:127642964 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.16 · 1 PDB
Residue 156: 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

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
LIMS2 p.Ala44Thr 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-ser156 (accessed [today's date]).

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