Is CRYGB p.Arg170= (c.510A>G) pathogenic?

CRYGB p.Arg170= (c.510A>G) is classified Likely benign in CRYGB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-28). Ultra-rare (popmax 0.0174%, mid); Associated with cataract 39 multiple types.

What condition is associated with CRYGB p.Arg170= (c.510A>G)?

CRYGB p.Arg170= (c.510A>G) is associated with cataract 39 multiple types (ClinVar).

How common is CRYGB p.Arg170= (c.510A>G) in the general population?

CRYGB p.Arg170= (c.510A>G) is ultra-rare (popmax 0.0174%, mid) (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.

CRYGB p.Arg170=

c.510A>G · VCV4738999

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0174%, mid)

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 -0.11	GERP -5, phastCons 0.73
Overall
CADD	6.372	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0174% Middle Eastern · 1/5,750 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000195% 3/1,541,700 alleles · ultra-rare exomes 2/1,389,558 · genomes 1/152,142 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0174%	5,750
European (non-Finnish)	0.000174%	574,884

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.Arg170=
Coding: c.510A>G
MANE Select: NM_005210
Type: single nucleotide variant
Location: chr2:208142656 (GRCh38)
Gene constraint: LOEUF 1.305 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.86 · 2 PDB
Residue 170: a β-strand; the beta/gamma crystallin 'greek key' 4 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.Arg170Gln Uncertain significance ★ same residue
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

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-arg170 (accessed [today's date]).

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