Is CRYBB2 p.Pro157= (c.471C>T) pathogenic?

CRYBB2 p.Pro157= (c.471C>T) is classified Pathogenic in CRYBB2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2007-03-01). Very rare (popmax 0.00933%, afr); Associated with cataract 3 multiple types.

What condition is associated with CRYBB2 p.Pro157= (c.471C>T)?

CRYBB2 p.Pro157= (c.471C>T) is associated with cataract 3 multiple types (ClinVar).

How common is CRYBB2 p.Pro157= (c.471C>T) in the general population?

CRYBB2 p.Pro157= (c.471C>T) is very rare (popmax 0.00933%, afr) (gnomAD).

CRYBB2 p.Pro157=

c.471C>T · rs745938679 · VCV16950

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00933%, afr)

Conditions

cataract 3 multiple types

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -3.7
Overall
CADD	0.237	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00933% African / African-American · 7/75,056 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00308%

Overall 0.00341% 55/1,614,172 alleles · very rare exomes 48/1,461,884 · genomes 7/152,288 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00933%	10,722
East Asian	0.00669%	14,957
European (non-Finnish)	0.00339%	29,500
Finnishnot grpmax-eligible	0.00312%	32,021
South Asian	0.0022%	45,542
Admixed American	0.00167%	60,020

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: CRYBB2
Protein: p.Pro157=
Coding: c.471C>T
MANE Select: NM_000496
dbSNP: rs745938679
Type: single nucleotide variant
Location: chr22:25231625 (GRCh38)
Gene constraint: LOEUF 0.765 · pLI 0.09 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 89.05 · 3 PDB
Residue 157: a UniProt-annotated variant site (in ctrct3); a turn; the beta/gamma crystallin 'greek key' 4 domain

Full CRYBB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cataract 3 multiple types — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CRYBB2 p.Pro157Leu Pathogenic ★ same residue
CRYBB2 p.Arg188Cys Pathogenic/Likely pathogenic ★★ same condition
CRYBB2 p.Arg188His Pathogenic ★★ same condition
CRYBB2 p.Gln155Ter Pathogenic/Likely pathogenic ★★ same condition
CRYBB2 p.Gly119Arg Pathogenic/Likely pathogenic ★★ same condition
CRYBB2 p.Arg160Pro Uncertain significance ★★ ⚠ same condition
CRYBB2 p.Gly57Glu Uncertain significance ★★ ⚠ same condition
CRYBB2 p.Gly61Ser Uncertain significance ★★ ⚠ same condition

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/crybb2-p-pro157 (accessed [today's date]).

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