Is CRYGB p.Pro64= (c.192T>C) pathogenic?

CRYGB p.Pro64= (c.192T>C) is classified Benign in CRYGB (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-28). Common (popmax 54.6%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with cataract 39 multiple types.

What condition is associated with CRYGB p.Pro64= (c.192T>C)?

CRYGB p.Pro64= (c.192T>C) is associated with cataract 39 multiple types (ClinVar).

How is Early onset non-syndromic cataract inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CRYGB p.Pro64=

Q: How common is CRYGB p.Pro64= (c.192T>C) in the general population?

CRYGB p.Pro64= (c.192T>C) is common (popmax 54.6%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.192T>C · rs2854723 · VCV677165

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 54.6%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

cataract 39 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 -6.1	GERP -5
Overall
CADD	0.231	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 54.6% European (non-Finnish) · 644,590/1,179,938 alleles

Filtering AF 54.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 54.5%

Overall 52.2% 841,826/1,613,698 alleles · common exomes 768,467/1,461,794 · genomes 73,359/151,904 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	62%	2
European (non-Finnish)grpmax	54.6%	2
South Asian	54.3%	2
Middle Eastern	53.4%	2
Remaining individualsnot grpmax-eligible	52%	2
Amishnot grpmax-eligible	50.9%	2
Finnishnot grpmax-eligible	48.8%	2
African / African-American	43.7%	2
Admixed American	32%	3
East Asian	22.6%	4

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CRYGB
Protein: p.Pro64=
Coding: c.192T>C
MANE Select: NM_005210
dbSNP: rs2854723
Type: single nucleotide variant
Location: chr2:208145834 (GRCh38)
Gene constraint: LOEUF 1.305 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.86 · 2 PDB
Residue 64: a β-strand; the beta/gamma crystallin 'greek key' 2 domain

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

Disease context

cataract 39 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

Similar variants

CRYGB p.Ala160Pro Uncertain significance ★★ ⚠ same condition
CRYGB p.Arg116His Uncertain significance ★★ ⚠ same condition
CRYGB p.Asp95Asn Uncertain significance ★★ ⚠ same condition
CRYGB p.Ile82Val Uncertain significance ★★ ⚠ same condition
CRYGB p.Pro84Leu Uncertain significance ★★ ⚠ same condition
CRYGB p.Ser16Asn Uncertain significance ★★ ⚠ same condition
CRYGB p.Arg59Trp Benign ★★ same condition
CRYGB p.Ile111Leu Benign ★★ 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/crygb-p-pro64 (accessed [today's date]).

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