Is LIMS2 p.Asp255= (c.765C>T) pathogenic?

LIMS2 p.Asp255= (c.765C>T) is classified Benign/Likely benign in LIMS2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-19). Rare (popmax 0.169%, eas); Associated with autosomal recessive limb-girdle muscular dystrophy type 2W.

What condition is associated with LIMS2 p.Asp255= (c.765C>T)?

LIMS2 p.Asp255= (c.765C>T) is associated with autosomal recessive limb-girdle muscular dystrophy type 2W (ClinVar).

How common is LIMS2 p.Asp255= (c.765C>T) in the general population?

LIMS2 p.Asp255= (c.765C>T) is rare (popmax 0.169%, eas) (gnomAD).

LIMS2 p.Asp255=

c.765C>T · rs199994172 · VCV475550

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.169%, 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.
REVEL	0.369	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4	GERP -3.7
Overall
CADD	2.135	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.169% East Asian · 76/44,868 alleles

Filtering AF 0.139% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.127%

Overall 0.00936% 151/1,612,978 alleles · rare exomes 127/1,460,682 · genomes 24/152,296 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.169%	590
Admixed American	0.0233%	4,287
Remaining individualsnot grpmax-eligible	0.016%	6,247
South Asian	0.011%	9,104
European (non-Finnish)	0.00347%	28,779

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.Asp255=
Coding: c.765C>T
MANE Select: NM_001161403
dbSNP: rs199994172
Type: single nucleotide variant
Location: chr2:127640307 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.16 · 1 PDB
Residue 255: the lim zinc-binding 4 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 p.Asp255Ala Uncertain significance ★ ⚠ same residue
LIMS2 p.Asp255fs Uncertain significance ★ same residue
LIMS2 p.Asp255Glu Uncertain significance ★ ⚠ 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

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-asp255 (accessed [today's date]).

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