Is LIM2 p.Gly8= (c.24C>T) pathogenic?

LIM2 p.Gly8= (c.24C>T) is classified Uncertain significance in LIM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Ultra-rare (popmax 0.0713%, eas); Associated with cataract 19 multiple types.

What condition is associated with LIM2 p.Gly8= (c.24C>T)?

LIM2 p.Gly8= (c.24C>T) is associated with cataract 19 multiple types (ClinVar).

How common is LIM2 p.Gly8= (c.24C>T) in the general population?

LIM2 p.Gly8= (c.24C>T) is ultra-rare (popmax 0.0713%, eas) (gnomAD).

How is Early onset non-syndromic cataract inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

LIM2 p.Gly8=

c.24C>T · rs147551022 · VCV893238

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0713%, eas)

Conditions

cataract 19 multiple types

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 4.5	GERP 1.2, phastCons 1
Overall
CADD	10.85	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0713% East Asian · 32/44,886 alleles

Filtering AF 0.0519% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0452%

Overall 0.00204% 33/1,614,096 alleles · ultra-rare exomes 32/1,461,734 · genomes 1/152,362 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0713%	1,403
European (non-Finnish)	8.47e-05%	1,180,027

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: LIM2
Protein: p.Gly8=
Coding: c.24C>T
MANE Select: NM_001161748
dbSNP: rs147551022
Type: single nucleotide variant
Location: chr19:51387420 (GRCh38)
Gene constraint: LOEUF 1.079 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.11 · 1 PDB
Residue 8: an α-helix

Full LIM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cataract 19 multiple types — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Early onset non-syndromic cataract (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Infancy, Neonatal

Similar variants

LIM2 p.Arg130Cys Pathogenic/Likely pathogenic ★★ same condition
LIM2 c.175+113G>C Uncertain significance ★★ same condition
LIM2 c.175+28G>A Uncertain significance ★★ same condition
LIM2 p.Ala153Thr Uncertain significance ★★ ⚠ same condition
LIM2 p.Arg129Cys Uncertain significance ★★ ⚠ same condition
LIM2 p.Arg162Trp Uncertain significance ★★ ⚠ same condition
LIM2 p.Arg167Gln Uncertain significance ★★ ⚠ same condition
LIM2 p.Arg168Cys 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/lim2-p-gly8 (accessed [today's date]).

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