Is LIM2 p.Ser77= (c.231C>T) pathogenic?

LIM2 p.Ser77= (c.231C>T) is classified Conflicting classifications of pathogenicity in LIM2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-22). Low-frequency (popmax 2.61%, afr); Associated with cataract 19 multiple types.

What condition is associated with LIM2 p.Ser77= (c.231C>T)?

LIM2 p.Ser77= (c.231C>T) is associated with cataract 19 multiple types (ClinVar).

How common is LIM2 p.Ser77= (c.231C>T) in the general population?

LIM2 p.Ser77= (c.231C>T) is low-frequency (popmax 2.61%, 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.Ser77=

c.231C>T · rs8111243 · VCV329974

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.61%, 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	all four deltas below 0.2 · G>T here scores Δ0.94 · evaluated, not missing
Constraint at this position
Conservation	phyloP -13	GERP -2.4
Overall
CADD	2.04	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.61% African / African-American · 1,958/74,974 alleles

Filtering AF 2.52% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.48%

Overall 0.843% 13,600/1,613,904 alleles · low-frequency exomes 11,802/1,461,748 · genomes 1,798/152,156 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.61%	38
Ashkenazi Jewishnot grpmax-eligible	1.38%	73
Remaining individualsnot grpmax-eligible	0.879%	114
European (non-Finnish)	0.822%	122
Middle Eastern	0.711%	141
Admixed American	0.697%	144
Finnishnot grpmax-eligible	0.542%	185
South Asian	0.191%	523
East Asian	0.00446%	22,437

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.Ser77=
Coding: c.231C>T
MANE Select: NM_001161748
dbSNP: rs8111243
Type: single nucleotide variant
Location: chr19:51382512 (GRCh38)
Gene constraint: LOEUF 1.079 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.11 · 1 PDB
Residue 77: 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-ser77 (accessed [today's date]).

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