Is CRYGD p.Ala64= (c.192C>G) pathogenic?

CRYGD p.Ala64= (c.192C>G) is classified Benign in CRYGD (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). Ultra-rare (popmax 0.01%, amr); Associated with cataract 4 multiple types.

What condition is associated with CRYGD p.Ala64= (c.192C>G)?

CRYGD p.Ala64= (c.192C>G) is associated with cataract 4 multiple types (ClinVar).

How common is CRYGD p.Ala64= (c.192C>G) in the general population?

CRYGD p.Ala64= (c.192C>G) is ultra-rare (popmax 0.01%, amr) (gnomAD).

CRYGD p.Ala64=

c.192C>G · rs766003243 · VCV897169

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

Conditions

cataract 4 multiple types

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -6.5	GERP -5
Overall
CADD	1.506	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.01% Admixed American · 6/59,986 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.000869% 14/1,611,550 alleles · ultra-rare exomes 12/1,459,364 · genomes 2/152,186 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	9,998
South Asian	0.0055%	18,198
Remaining individualsnot grpmax-eligible	0.0016%	62,310
European (non-Finnish)	0.00017%	589,946

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.Ala64=
Coding: c.192C>G
MANE Select: NM_006891
dbSNP: rs766003243
Type: single nucleotide variant
Location: chr2:208124172 (GRCh38)
Gene constraint: LOEUF 1.796 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.45 · 16 PDB
Residue 64: a UniProt-annotated variant site (in ctrct4; uncertain significance); the beta/gamma crystallin 'greek key' 2 domain; a β-strand

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-ala64 (accessed [today's date]).

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