Is CRYGC p.Pro28= (c.84G>A) pathogenic?

CRYGC p.Pro28= (c.84G>A) is classified Benign/Likely benign in CRYGC (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-01). Rare (popmax 0.858%, mid); Associated with Nuclear pulverulent cataract.

What condition is associated with CRYGC p.Pro28= (c.84G>A)?

CRYGC p.Pro28= (c.84G>A) is associated with Nuclear pulverulent cataract (ClinVar).

How common is CRYGC p.Pro28= (c.84G>A) in the general population?

CRYGC p.Pro28= (c.84G>A) is rare (popmax 0.858%, mid) (gnomAD).

CRYGC p.Pro28=

c.84G>A · rs142890808 · VCV704390

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.858%, mid)

Conditions

Nuclear pulverulent cataract

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 1.3	GERP 1.6, phastCons 1
Overall
CADD	14.85	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.858% Middle Eastern · 52/6,062 alleles

Filtering AF 0.672% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.605%

Overall 0.0352% 568/1,614,228 alleles · rare exomes 516/1,461,894 · genomes 52/152,334 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.858%	117
Ashkenazi Jewishnot grpmax-eligible	0.564%	177
Remaining individualsnot grpmax-eligible	0.0736%	1,359
Admixed American	0.0433%	2,309
European (non-Finnish)	0.0222%	4,504
African / African-American	0.0173%	5,774
East Asian	0.00223%	44,886
South Asian	0.0011%	91,086

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: CRYGC
Protein: p.Pro28=
Coding: c.84G>A
MANE Select: NM_020989
dbSNP: rs142890808
Type: single nucleotide variant
Location: chr2:208129609 (GRCh38)
Gene constraint: LOEUF 0.941 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 96.66 · 1 PDB
Residue 28: a turn; the beta/gamma crystallin 'greek key' 1 domain

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

Disease context

Nuclear pulverulent cataract — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CRYGC p.Pro28Leu Uncertain significance ★ ⚠ same residue
CRYGC p.Arg122His Uncertain significance ★★ ⚠ same condition
CRYGC p.Arg15His Uncertain significance ★★ ⚠ same condition
CRYGC p.Arg77Cys Uncertain significance ★★ ⚠ same condition
CRYGC p.Glu150Asp Uncertain significance ★★ ⚠ same condition
CRYGC p.Pro49Thr Uncertain significance ★★ ⚠ same condition
CRYGC c.10-10T>C Benign/Likely benign ★★ same condition
CRYGC p.Gly41= 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/crygc-p-pro28 (accessed [today's date]).

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