Is LIMS2 p.Cys79= (c.237C>T) pathogenic?

LIMS2 p.Cys79= (c.237C>T) is classified Uncertain significance in LIMS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-17). Ultra-rare (popmax 0.0176%, sas); Associated with autosomal recessive limb-girdle muscular dystrophy type 2W.

What condition is associated with LIMS2 p.Cys79= (c.237C>T)?

LIMS2 p.Cys79= (c.237C>T) is associated with autosomal recessive limb-girdle muscular dystrophy type 2W (ClinVar).

How common is LIMS2 p.Cys79= (c.237C>T) in the general population?

LIMS2 p.Cys79= (c.237C>T) is ultra-rare (popmax 0.0176%, sas) (gnomAD).

LIMS2 p.Cys79=

c.237C>T · rs531118175 · VCV1046324

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0176%, sas)

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.
REVEL	0.209	benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -4.1	GERP -3.5
Overall
CADD	4.461	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0176% South Asian · 16/91,090 alleles

Filtering AF 0.011% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00888%

Overall 0.00223% 36/1,614,054 alleles · ultra-rare exomes 33/1,461,718 · genomes 3/152,336 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0176%	5,693
African / African-American	0.00533%	18,763
Remaining individualsnot grpmax-eligible	0.0048%	20,833
Finnishnot grpmax-eligible	0.00313%	31,984
East Asian	0.00223%	44,892
European (non-Finnish)	0.000847%	117,996

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.Cys79=
Coding: c.237C>T
MANE Select: NM_001161403
dbSNP: rs531118175
Type: single nucleotide variant
Location: chr2:127654831 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.16 · 1 PDB
Residue 79: the lim zinc-binding 2 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-cys79 (accessed [today's date]).

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