Is LIM2 p.Arg162Trp (c.484C>T) pathogenic?

LIM2 p.Arg162Trp (c.484C>T) is classified Uncertain significance in LIM2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-01). AlphaMissense: likely benign (0.1986); Ultra-rare (popmax 0.0166%, mid); Associated with Inborn genetic diseases.

What condition is associated with LIM2 p.Arg162Trp (c.484C>T)?

LIM2 p.Arg162Trp (c.484C>T) is associated with Inborn genetic diseases, cataract 19 multiple types (ClinVar).

How common is LIM2 p.Arg162Trp (c.484C>T) in the general population?

LIM2 p.Arg162Trp (c.484C>T) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

What do computational predictors say about LIM2 p.Arg162Trp (c.484C>T)?

AlphaMissense predicts likely benign (score 0.1986) — an in-silico prediction, not a clinical call.

LIM2 p.Arg162Trp

c.484C>T · rs558484735 · VCV1029169

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1986 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1986	likely benign
REVEL	0.783	moderately pathogenic-leaning
SaProt	LLR -8.46	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.77 · evaluated, not missing
Constraint at this position
Conservation	phyloP 9.6	GERP 1.5, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 7,239 bp · p 0.39 · regional, not allelic
Overall
CADD	27.9	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 0.0166% Middle Eastern · 1/6,026 alleles

Filtering AF 0.00429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.00205% 33/1,613,586 alleles · ultra-rare exomes 28/1,461,468 · genomes 5/152,118 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,026
Admixed American	0.01%	9,990
South Asian	0.0044%	22,750
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,588
European (non-Finnish)	0.00161%	62,097
Remaining individualsnot grpmax-eligible	0.0016%	62,484
African / African-American	0.00133%	74,932

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.Arg162Trp
Coding: c.484C>T
MANE Select: NM_001161748
dbSNP: rs558484735
Type: single nucleotide variant
Location: chr19:51380239 (GRCh38)
Gene constraint: LOEUF 1.079 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.11 · 1 PDB
Residue 162: an α-helix

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.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.Arg167Gln Uncertain significance ★★ ⚠ same condition
LIM2 p.Arg168Cys Uncertain significance ★★ ⚠ same condition
LIM2 p.Arg44Gln 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-arg162trp (accessed [today's date]).

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