Is LIM2 p.Arg130Cys (c.388C>T) pathogenic?

LIM2 p.Arg130Cys (c.388C>T) is classified Pathogenic/Likely pathogenic in LIM2 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2023-11-27). AlphaMissense: ambiguous (0.4518); No allele count reported in gnomAD v4.1 (AN 1,614,182); Associated with LIM2-related disorder.

What condition is associated with LIM2 p.Arg130Cys (c.388C>T)?

LIM2 p.Arg130Cys (c.388C>T) is associated with LIM2-related disorder, cataract, cataract 19 multiple types (ClinVar).

How common is LIM2 p.Arg130Cys (c.388C>T) in the general population?

LIM2 p.Arg130Cys (c.388C>T) is no allele count reported in gnomAD v4.1 (AN 1,614,182) (gnomAD).

What do computational predictors say about LIM2 p.Arg130Cys (c.388C>T)?

AlphaMissense predicts ambiguous (score 0.4518) — an in-silico prediction, not a clinical call.

LIM2 p.Arg130Cys

c.388C>T · rs1568480054 · VCV625113

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

ambiguous

0.4518 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,614,182)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

LIM2-related disorder

Computational evidence

Protein change
AlphaMissense	0.4518	ambiguous
REVEL	0.885	moderately pathogenic-leaning
SaProt	LLR -10.14	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.6	GERP 1.2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 7,239 bp · p 0.39 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,614,182). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: LIM2
Protein: p.Arg130Cys
Coding: c.388C>T
MANE Select: NM_001161748
dbSNP: rs1568480054
Type: single nucleotide variant
Location: chr19:51380577 (GRCh38)
Gene constraint: LOEUF 1.079 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.11 · 1 PDB
Residue 130: a β-strand

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

Disease context

LIM2-related disorder

Also linked: cataract cataract 19 multiple types

Similar variants

LIM2 p.Arg130del Uncertain significance ★ same residue
LIM2 p.Arg130His Uncertain significance ★ ⚠ same residue
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

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-arg130cys (accessed [today's date]).

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