Is CRYGD c.252+7A>G pathogenic?

CRYGD c.252+7A>G is classified Benign in CRYGD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-08-17). Ultra-rare (popmax 0.0442%, mid); Associated with cataract 4 multiple types.

What condition is associated with CRYGD c.252+7A>G?

CRYGD c.252+7A>G is associated with cataract 4 multiple types (ClinVar).

How common is CRYGD c.252+7A>G in the general population?

CRYGD c.252+7A>G is ultra-rare (popmax 0.0442%, mid) (gnomAD).

CRYGD c.252+7A>G

rs185860020 · VCV333873

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0442%, mid)

Conditions

cataract 4 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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2	GERP -3.8
Overall
CADD	3.262	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0442% Middle Eastern · 2/4,520 alleles

Filtering AF 0.0351% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0339%

Overall 0.154% 2,474/1,611,668 alleles · ultra-rare exomes 2,105/1,459,368 · genomes 369/152,300 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	3%	33
Remaining individualsnot grpmax-eligible	0.128%	779
Middle Easterngrpmax	0.0442%	2,260
European (non-Finnish)	0.0381%	2,628
Admixed American	0.0283%	3,530
African / African-American	0.016%	6,248
South Asian	0.0044%	22,744
East Asian	0.00223%	44,882

Finnish 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
Coding: c.252+7A>G
MANE Select: NM_006891
dbSNP: rs185860020
Type: single nucleotide variant
Location: chr2:208124105 (GRCh38)
Gene constraint: LOEUF 1.796 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.45 · 16 PDB

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.-40C>T Benign ★★ same condition
CRYGD c.*12T>C 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-c-252-plus-7a-g (accessed [today's date]).

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