Is CRYBA4 p.Pro155= (c.465G>A) pathogenic?

CRYBA4 p.Pro155= (c.465G>A) is classified Benign/Likely benign in CRYBA4 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-11-06). Rare (popmax 0.203%, nfe); Associated with cataract 23.

What condition is associated with CRYBA4 p.Pro155= (c.465G>A)?

CRYBA4 p.Pro155= (c.465G>A) is associated with cataract 23 (ClinVar).

How common is CRYBA4 p.Pro155= (c.465G>A) in the general population?

CRYBA4 p.Pro155= (c.465G>A) is rare (popmax 0.203%, nfe) (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.

CRYBA4 p.Pro155=

c.465G>A · rs117467748 · VCV702372

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.203%, nfe)

Conditions

cataract 23

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 -13	GERP -3.8
Overall
CADD	3.456	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.203% European (non-Finnish) · 2,397/1,180,016 alleles

Filtering AF 0.196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.194%

Overall 0.165% 2,661/1,614,190 alleles · rare exomes 2,493/1,461,842 · genomes 168/152,348 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.203%	492
Admixed American	0.153%	652
Remaining individualsnot grpmax-eligible	0.117%	856
Ashkenazi Jewishnot grpmax-eligible	0.108%	925
Middle Eastern	0.099%	1,010
East Asian	0.0379%	2,640
Finnishnot grpmax-eligible	0.0359%	2,784
African / African-American	0.024%	4,170
South Asian	0.00329%	30,357

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: CRYBA4
Protein: p.Pro155=
Coding: c.465G>A
MANE Select: NM_001886
dbSNP: rs117467748
Type: single nucleotide variant
Location: chr22:26630361 (GRCh38)
Gene constraint: LOEUF 1.238 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.64 · 1 PDB
Residue 155: a turn; the beta/gamma crystallin 'greek key' 4 domain

Full CRYBA4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cataract 23 — 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

CRYBA4 p.Pro155Leu Uncertain significance ★ ⚠ same residue
CRYBA4 p.Phe22Ser Uncertain significance ★★ ⚠ same condition
CRYBA4 p.Phe57Val Uncertain significance ★★ ⚠ same condition
CRYBA4 c.159-20A>G Benign ★★ same condition
CRYBA4 c.300+3A>G Benign ★★ same condition
CRYBA4 c.40-1G>C Benign/Likely benign ★★ same condition
CRYBA4 c.444-18G>A Benign ★★ same condition
CRYBA4 p.Arg103Cys Benign/Likely 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/cryba4-p-pro155 (accessed [today's date]).

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