Is CRYBB1 p.Leu239= (c.717C>T) pathogenic?

CRYBB1 p.Leu239= (c.717C>T) is classified Likely benign in CRYBB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-18). Ultra-rare (popmax 0.02%, amr); Associated with cataract 17 multiple types.

What condition is associated with CRYBB1 p.Leu239= (c.717C>T)?

CRYBB1 p.Leu239= (c.717C>T) is associated with cataract 17 multiple types (ClinVar).

How common is CRYBB1 p.Leu239= (c.717C>T) in the general population?

CRYBB1 p.Leu239= (c.717C>T) is ultra-rare (popmax 0.02%, amr) (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.

CRYBB1 p.Leu239=

c.717C>T · rs779509832 · VCV1531127

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, amr)

Conditions

cataract 17 multiple types

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -8.7	GERP -3.7
Overall
CADD	0.102	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.02% Admixed American · 12/60,008 alleles

Filtering AF 0.0115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00898%

Overall 0.00204% 33/1,613,712 alleles · ultra-rare exomes 27/1,461,446 · genomes 6/152,266 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.02%	5,001
South Asian	0.00659%	15,178
Remaining individualsnot grpmax-eligible	0.0016%	62,450
African / African-American	0.00133%	74,950
European (non-Finnish)	0.0011%	90,773

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: CRYBB1
Protein: p.Leu239=
Coding: c.717C>T
MANE Select: NM_001887
dbSNP: rs779509832
Type: single nucleotide variant
Location: chr22:26599532 (GRCh38)

Full CRYBB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cataract 17 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

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/crybb1-p-leu239 (accessed [today's date]).

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