Is CRYBA1 c.357+7C>T pathogenic?

CRYBA1 c.357+7C>T is classified Likely benign in CRYBA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-19). Very rare (popmax 0.00167%, amr); Associated with cataract 10 multiple types.

What condition is associated with CRYBA1 c.357+7C>T?

CRYBA1 c.357+7C>T is associated with cataract 10 multiple types (ClinVar).

How common is CRYBA1 c.357+7C>T in the general population?

CRYBA1 c.357+7C>T is very rare (popmax 0.00167%, amr) (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 c.357+7C>T

rs1473744071 · VCV1635540

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

cataract 10 multiple types

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +7	near-intronic (+7 nt from the splice site) · inside the BP7-excluded zone
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.31 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.41	GERP 1.9, phastCons 0.94
Overall
CADD	9.81	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,016 alleles

Overall 6.84e-05% 1/1,461,796 alleles · very rare

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
Coding: c.357+7C>T
MANE Select: NM_005208
dbSNP: rs1473744071
Type: single nucleotide variant
Location: chr17:29252212 (GRCh38)
Gene constraint: LOEUF 0.987 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.27

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 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
CRYBA1 c.97-8C>T 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/cryba1-c-357-plus-7c-t (accessed [today's date]).

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