Is CRYBB1 p.Ala52= (c.156G>A) pathogenic?

CRYBB1 p.Ala52= (c.156G>A) is classified Conflicting classifications of pathogenicity in CRYBB1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-07-29). Rare (popmax 0.148%, mid); Associated with cataract 17 multiple types.

What condition is associated with CRYBB1 p.Ala52= (c.156G>A)?

CRYBB1 p.Ala52= (c.156G>A) is associated with cataract 17 multiple types (ClinVar).

How common is CRYBB1 p.Ala52= (c.156G>A) in the general population?

CRYBB1 p.Ala52= (c.156G>A) is rare (popmax 0.148%, mid) (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.Ala52=

c.156G>A · rs149902597 · VCV341049

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.148%, mid)

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 -2.3	GERP -4.3
Overall
CADD	5.565	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.148% Middle Eastern · 9/6,062 alleles

Filtering AF 0.0955% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0937%

Overall 0.0898% 1,449/1,614,174 alleles · rare exomes 1,317/1,461,860 · genomes 132/152,314 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.148%	674
European (non-Finnish)	0.1%	997
African / African-American	0.0879%	1,137
South Asian	0.0867%	1,153
Remaining individualsnot grpmax-eligible	0.0736%	1,359
Admixed American	0.0533%	1,876
Finnishnot grpmax-eligible	0.05%	2,001
East Asian	0.00223%	44,866

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.Ala52=
Coding: c.156G>A
MANE Select: NM_001887
dbSNP: rs149902597
Type: single nucleotide variant
Location: chr22:26616164 (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-ala52 (accessed [today's date]).

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