Is CRYBB2 p.Gly45= (c.135C>T) pathogenic?

CRYBB2 p.Gly45= (c.135C>T) is classified Likely benign in CRYBB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-10). Very rare (popmax 0.00267%, afr); Associated with cataract 3 multiple types.

What condition is associated with CRYBB2 p.Gly45= (c.135C>T)?

CRYBB2 p.Gly45= (c.135C>T) is associated with cataract 3 multiple types (ClinVar).

How common is CRYBB2 p.Gly45= (c.135C>T) in the general population?

CRYBB2 p.Gly45= (c.135C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

CRYBB2 p.Gly45=

c.135C>T · rs768007526 · VCV2994338

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

cataract 3 multiple types

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -11	GERP -3.1
Overall
CADD	6.841	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,876 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000496% 8/1,612,354 alleles · very rare exomes 6/1,460,164 · genomes 2/152,190 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,438
East Asian	0.00223%	44,890
European (non-Finnish)	0.000424%	235,688

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: CRYBB2
Protein: p.Gly45=
Coding: c.135C>T
MANE Select: NM_000496
dbSNP: rs768007526
Type: single nucleotide variant
Location: chr22:25224998 (GRCh38)
Gene constraint: LOEUF 0.765 · pLI 0.09 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 89.05 · 3 PDB
Residue 45: the beta/gamma crystallin 'greek key' 1 domain

Full CRYBB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cataract 3 multiple types — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CRYBB2 p.Arg188Cys Pathogenic/Likely pathogenic ★★ same condition
CRYBB2 p.Arg188His Pathogenic ★★ same condition
CRYBB2 p.Gln155Ter Pathogenic/Likely pathogenic ★★ same condition
CRYBB2 p.Gly119Arg Pathogenic/Likely pathogenic ★★ same condition
CRYBB2 p.Arg160Pro Uncertain significance ★★ ⚠ same condition
CRYBB2 p.Gly57Glu Uncertain significance ★★ ⚠ same condition
CRYBB2 p.Gly61Ser Uncertain significance ★★ ⚠ same condition
CRYBB2 c.449+9G>A Benign ★★ 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/crybb2-p-gly45 (accessed [today's date]).

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