Is CRYBB1 p.Ter253Arg (c.757T>C) pathogenic?

CRYBB1 p.Ter253Arg (c.757T>C) is classified Uncertain significance in CRYBB1 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-07-28). Very rare (popmax 8.48e-05%, nfe); Associated with cataract 17 multiple types.

What condition is associated with CRYBB1 p.Ter253Arg (c.757T>C)?

CRYBB1 p.Ter253Arg (c.757T>C) is associated with cataract 17 multiple types (ClinVar).

How common is CRYBB1 p.Ter253Arg (c.757T>C) in the general population?

CRYBB1 p.Ter253Arg (c.757T>C) is very rare (popmax 8.48e-05%, nfe) (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.Ter253Arg

c.757T>C · rs1114167432 · VCV427748

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

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.
Consequence	stop-loss	predicted loss-of-function
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Overall
CADD	16.69	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,500 alleles

Overall 6.2e-05% 1/1,612,140 alleles · very rare exomes 1/1,459,814 · genomes 0/152,326 · joint denominator

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.Ter253Arg
Coding: c.757T>C
MANE Select: NM_001887
dbSNP: rs1114167432
Type: single nucleotide variant
Location: chr22:26599492 (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-ter253arg (accessed [today's date]).

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