Is CRYGS p.Ile8= (c.24T>A) pathogenic?

CRYGS p.Ile8= (c.24T>A) is classified Benign in CRYGS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-31). Low-frequency (popmax 1.17%, afr); Associated with cataract 20 multiple types.

What condition is associated with CRYGS p.Ile8= (c.24T>A)?

CRYGS p.Ile8= (c.24T>A) is associated with cataract 20 multiple types (ClinVar).

How common is CRYGS p.Ile8= (c.24T>A) in the general population?

CRYGS p.Ile8= (c.24T>A) is low-frequency (popmax 1.17%, 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.

CRYGS p.Ile8=

c.24T>A · rs113031838 · VCV530955

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.17%, afr)

Conditions

cataract 20 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 -0.084	GERP -5.3, phastCons 0.009
Overall
CADD	7.805	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.17% African / African-American · 877/75,050 alleles

Filtering AF 1.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.08%

Overall 0.061% 985/1,614,016 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.17%	86
Remaining individualsnot grpmax-eligible	0.0992%	1,008
Admixed American	0.055%	1,819
South Asian	0.00659%	15,179
European (non-Finnish)	0.000593%	168,554

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: CRYGS
Protein: p.Ile8=
Coding: c.24T>A
MANE Select: NM_017541
dbSNP: rs113031838
Type: single nucleotide variant
Location: chr3:186539595 (GRCh38)
Gene constraint: LOEUF 0.881 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 95.63 · 12 PDB
Residue 8: the beta/gamma crystallin 'greek key' 1 domain; a β-strand

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

Disease context

cataract 20 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

CRYGS p.Ile8Asn Likely pathogenic ★ same residue
CRYGS p.Arg125Gln Uncertain significance ★★ ⚠ same condition
CRYGS p.Arg36His Uncertain significance ★★ ⚠ same condition
CRYGS p.Glu100Ala Uncertain significance ★★ ⚠ same condition
CRYGS p.Gly102= Benign/Likely benign ★★ same condition
CRYGS p.Gly102Glu Likely benign ★★ same condition
CRYGS p.Gly18Asp Pathogenic ★ same condition
CRYGS p.Gly18Val Pathogenic ★ 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/crygs-p-ile8 (accessed [today's date]).

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