Is CRYBB1 p.Ala98= (c.294G>A) pathogenic?

CRYBB1 p.Ala98= (c.294G>A) is classified Uncertain significance in CRYBB1 (ClinVar, Single submitter, 3 submitters; last evaluated 2018-01-13). Ultra-rare (popmax 0.0869%, eas); Associated with cataract 17 multiple types.

What condition is associated with CRYBB1 p.Ala98= (c.294G>A)?

CRYBB1 p.Ala98= (c.294G>A) is associated with cataract 17 multiple types (ClinVar).

How common is CRYBB1 p.Ala98= (c.294G>A) in the general population?

CRYBB1 p.Ala98= (c.294G>A) is ultra-rare (popmax 0.0869%, eas) (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.Ala98=

c.294G>A · rs760235124 · VCV901777

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0869%, eas)

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 -15	GERP -4.6
Overall
CADD	0.383	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0869% East Asian · 39/44,854 alleles

Filtering AF 0.0653% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0578%

Overall 0.00372% 60/1,611,372 alleles · ultra-rare exomes 59/1,459,416 · genomes 1/151,956 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0869%	1,150
Admixed American	0.00333%	29,990
Finnishnot grpmax-eligible	0.00157%	63,694
European (non-Finnish)	0.00144%	69,298
African / African-American	0.00134%	74,790

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.Ala98=
Coding: c.294G>A
MANE Select: NM_001887
dbSNP: rs760235124
Type: single nucleotide variant
Location: chr22:26612077 (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-ala98 (accessed [today's date]).

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