Is LIM2 p.Cys74= (c.222C>T) pathogenic?

LIM2 p.Cys74= (c.222C>T) is classified Likely benign in LIM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-05). Ultra-rare (popmax 0.0561%, afr); Associated with cataract 19 multiple types.

What condition is associated with LIM2 p.Cys74= (c.222C>T)?

LIM2 p.Cys74= (c.222C>T) is associated with cataract 19 multiple types (ClinVar).

How common is LIM2 p.Cys74= (c.222C>T) in the general population?

LIM2 p.Cys74= (c.222C>T) is ultra-rare (popmax 0.0561%, afr) (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.Cys74=

c.222C>T · rs200121972 · VCV2799612

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0561%, afr)

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	GERP -2.4
Overall
CADD	1.846	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0561% African / African-American · 42/74,884 alleles

Filtering AF 0.0426% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0379%

Overall 0.0133% 215/1,613,784 alleles · ultra-rare exomes 181/1,461,684 · genomes 34/152,100 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0561%	1,783
Remaining individualsnot grpmax-eligible	0.0176%	5,678
Middle Eastern	0.0165%	6,056
European (non-Finnish)	0.0126%	7,919
South Asian	0.00769%	13,011
Admixed American	0.005%	19,993
East Asian	0.00446%	22,444

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.Cys74=
Coding: c.222C>T
MANE Select: NM_001161748
dbSNP: rs200121972
Type: single nucleotide variant
Location: chr19:51382521 (GRCh38)
Gene constraint: LOEUF 1.079 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.11 · 1 PDB
Residue 74: 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-cys74 (accessed [today's date]).

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