Is CRYGD p.Arg95= (c.285A>G) pathogenic?

CRYGD p.Arg95= (c.285A>G) is classified Benign in CRYGD (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-01). Common (popmax 92.4%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with cataract 4 multiple types.

What condition is associated with CRYGD p.Arg95= (c.285A>G)?

CRYGD p.Arg95= (c.285A>G) is associated with cataract 4 multiple types (ClinVar).

CRYGD p.Arg95=

Q: How common is CRYGD p.Arg95= (c.285A>G) in the general population?

CRYGD p.Arg95= (c.285A>G) is common (popmax 92.4%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.285A>G · rs2305430 · VCV260061

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 92.4%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

cataract 4 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 -4.9	GERP -3.7
Overall
CADD	7.773	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 92.4% European (non-Finnish) · 1,089,900/1,180,010 alleles

Filtering AF 92.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 92.2%

Overall 89.4% 1,442,439/1,614,034 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	97.1%	1
European (non-Finnish)grpmax	92.4%	1
Finnishnot grpmax-eligible	92.3%	1
Remaining individualsnot grpmax-eligible	87.3%	1
Ashkenazi Jewishnot grpmax-eligible	85.8%	1
African / African-American	84.4%	1
Middle Eastern	82.6%	1
South Asian	79.6%	1
Admixed American	77.9%	1
East Asian	56.1%	2

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CRYGD
Protein: p.Arg95=
Coding: c.285A>G
MANE Select: NM_006891
dbSNP: rs2305430
Type: single nucleotide variant
Location: chr2:208121913 (GRCh38)
Gene constraint: LOEUF 1.796 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.45 · 16 PDB
Residue 95: a UniProt-annotated variant site (in ctrct4; uncertain significance); a β-strand; the beta/gamma crystallin 'greek key' 3 domain

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

Disease context

cataract 4 multiple types — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CRYGD p.Arg140Ter Pathogenic ★★ same condition
CRYGD p.Arg15Cys Pathogenic ★★ ⚠ same condition
CRYGD p.Pro24Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
CRYGD p.Asn161Ser Uncertain significance ★★ ⚠ same condition
CRYGD c.10-7C>G Benign ★★ same condition
CRYGD c.252+10T>A Benign/Likely benign ★★ same condition
CRYGD c.252+7A>G Benign ★★ same condition
CRYGD c.-40C>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/crygd-p-arg95 (accessed [today's date]).

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