Is CRYGC p.Arg142Gln (c.425G>A) pathogenic?

CRYGC p.Arg142Gln (c.425G>A) is classified Uncertain significance in CRYGC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-21). AlphaMissense: likely benign (0.1363); Very rare (popmax 0.00439%, sas); Associated with Nuclear pulverulent cataract.

What condition is associated with CRYGC p.Arg142Gln (c.425G>A)?

CRYGC p.Arg142Gln (c.425G>A) is associated with Nuclear pulverulent cataract (ClinVar).

How common is CRYGC p.Arg142Gln (c.425G>A) in the general population?

CRYGC p.Arg142Gln (c.425G>A) is very rare (popmax 0.00439%, sas) (gnomAD).

What do computational predictors say about CRYGC p.Arg142Gln (c.425G>A)?

AlphaMissense predicts likely benign (score 0.1363) — an in-silico prediction, not a clinical call.

CRYGC p.Arg142Gln

c.425G>A · VCV4754405

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1363 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Nuclear pulverulent cataract

Computational evidence

Protein change
AlphaMissense	0.1363	likely benign
REVEL	0.296	indeterminate
SaProt	LLR -10.98	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.32	GERP 2.5
Regional constraint	o/e 1.00	unconstrained · MANE · 1,586 bp · p 0.96 · regional, not allelic
Overall
CADD	19.28	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00439% South Asian · 4/91,088 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00192% 31/1,614,112 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,772
Remaining individualsnot grpmax-eligible	0.0032%	31,244
European (non-Finnish)	0.00203%	49,169
Admixed American	0.00167%	60,012

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.Arg142Gln
Coding: c.425G>A
MANE Select: NM_020989
Type: single nucleotide variant
Location: chr2:208128303 (GRCh38)
Gene constraint: LOEUF 0.941 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 96.66 · 1 PDB
Residue 142: a β-strand; the beta/gamma crystallin 'greek key' 4 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.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
CRYGC p.Pro28= Benign/Likely 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-arg142gln (accessed [today's date]).

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