Is CRYBB1 p.Pro100= (c.300C>T) pathogenic?

CRYBB1 p.Pro100= (c.300C>T) is classified Conflicting classifications of pathogenicity in CRYBB1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-06-02). Ultra-rare (popmax 0.0165%, mid); Associated with Inborn genetic diseases.

What condition is associated with CRYBB1 p.Pro100= (c.300C>T)?

CRYBB1 p.Pro100= (c.300C>T) is associated with Inborn genetic diseases, cataract 17 multiple types (ClinVar).

How common is CRYBB1 p.Pro100= (c.300C>T) in the general population?

CRYBB1 p.Pro100= (c.300C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

CRYBB1 p.Pro100=

c.300C>T · rs140515221 · VCV2191216

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

Inborn genetic diseases

⚠ 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 1	phastCons 1
Overall
CADD	14.97	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.0138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.013%

Overall 0.0124% 200/1,614,160 alleles · ultra-rare exomes 178/1,461,816 · genomes 22/152,344 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
European (non-Finnish)	0.0156%	6,413
Remaining individualsnot grpmax-eligible	0.0096%	10,418
Admixed American	0.00833%	12,005
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
South Asian	0.0022%	45,544
African / African-American	0.00133%	75,066

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.Pro100=
Coding: c.300C>T
MANE Select: NM_001887
dbSNP: rs140515221
Type: single nucleotide variant
Location: chr22:26608021 (GRCh38)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cataract 17 multiple types

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-pro100 (accessed [today's date]).

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