Is CRYBA1 p.Pro25= (c.75G>A) pathogenic?

CRYBA1 p.Pro25= (c.75G>A) is classified Benign in CRYBA1 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-04-26). Rare (popmax 0.123%, afr); Associated with cataract 10 multiple types.

What condition is associated with CRYBA1 p.Pro25= (c.75G>A)?

CRYBA1 p.Pro25= (c.75G>A) is associated with cataract 10 multiple types (ClinVar).

How common is CRYBA1 p.Pro25= (c.75G>A) in the general population?

CRYBA1 p.Pro25= (c.75G>A) is rare (popmax 0.123%, afr) (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.

CRYBA1 p.Pro25=

c.75G>A · rs368469355 · VCV1166238

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.123%, afr)

Conditions

cataract 10 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 0.013	GERP -4, phastCons 0.23
Overall
CADD	10.62	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.123% African / African-American · 92/74,816 alleles

Filtering AF 0.103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0951%

Overall 0.00738% 119/1,611,918 alleles · rare exomes 62/1,460,050 · genomes 57/151,868 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.123%	813
Remaining individualsnot grpmax-eligible	0.00961%	10,403
Admixed American	0.00667%	14,989
European (non-Finnish)	0.00144%	69,313

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: CRYBA1
Protein: p.Pro25=
Coding: c.75G>A
MANE Select: NM_005208
dbSNP: rs368469355
Type: single nucleotide variant
Location: chr17:29249185 (GRCh38)
Gene constraint: LOEUF 0.987 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.27
Residue 25: the 'n-terminal arm' region; the 'disordered' region

Full CRYBA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cataract 10 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

CRYBA1 p.Pro25Leu Benign/Likely benign ★★ same residue
CRYBA1 c.215+1G>A Pathogenic/Likely pathogenic ★★ same condition
CRYBA1 c.215+1G>T Pathogenic/Likely pathogenic ★★ same condition
CRYBA1 c.500+1G>A Likely pathogenic ★★ same condition
CRYBA1 p.Arg109His Uncertain significance ★★ ⚠ same condition
CRYBA1 p.Glu39Asp Uncertain significance ★★ same condition
CRYBA1 p.Leu183Ter Uncertain significance ★★ same condition
CRYBA1 c.215+16C>T 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/cryba1-p-pro25 (accessed [today's date]).

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