Is LIM2 p.Arg44Trp (c.130C>T) pathogenic?

LIM2 p.Arg44Trp (c.130C>T) is classified Uncertain significance in LIM2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-29). AlphaMissense: ambiguous (0.442); Very rare (popmax 0.00878%, sas); Associated with Inborn genetic diseases.

What condition is associated with LIM2 p.Arg44Trp (c.130C>T)?

LIM2 p.Arg44Trp (c.130C>T) is associated with Inborn genetic diseases, cataract 19 multiple types (ClinVar).

How common is LIM2 p.Arg44Trp (c.130C>T) in the general population?

LIM2 p.Arg44Trp (c.130C>T) is very rare (popmax 0.00878%, sas) (gnomAD).

What do computational predictors say about LIM2 p.Arg44Trp (c.130C>T)?

AlphaMissense predicts ambiguous (score 0.442) — an in-silico prediction, not a clinical call.

LIM2 p.Arg44Trp

c.130C>T · rs374509682 · VCV2459542

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.442 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00878%, sas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.442	ambiguous
REVEL	0.818	moderately pathogenic-leaning
SaProt	LLR -11.28	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 8.6	GERP 1.2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 7,239 bp · p 0.39 · regional, not allelic
Overall
CADD	29.6	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

Grpmax group 0.00878% South Asian · 8/91,088 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00372%

Overall 0.00477% 77/1,614,016 alleles · very rare exomes 73/1,461,816 · genomes 4/152,200 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00878%	11,386
European (non-Finnish)	0.00517%	19,345
Remaining individualsnot grpmax-eligible	0.0048%	20,827
East Asian	0.00445%	22,448
Admixed American	0.00333%	30,006
African / African-American	0.00133%	74,916

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.Arg44Trp
Coding: c.130C>T
MANE Select: NM_001161748
dbSNP: rs374509682
Type: single nucleotide variant
Location: chr19:51387314 (GRCh38)
Gene constraint: LOEUF 1.079 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.11 · 1 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cataract 19 multiple types

Similar variants

LIM2 p.Arg44Gln Uncertain significance ★★ ⚠ same residue
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

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-arg44trp (accessed [today's date]).

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