Is CRYGD p.Arg80= (c.240C>T) pathogenic?

CRYGD p.Arg80= (c.240C>T) is classified Likely benign in CRYGD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-07-09). Rare (popmax 0.332%, mid); Associated with Aculeiform cataract.

What condition is associated with CRYGD p.Arg80= (c.240C>T)?

CRYGD p.Arg80= (c.240C>T) is associated with Aculeiform cataract (ClinVar).

How common is CRYGD p.Arg80= (c.240C>T) in the general population?

CRYGD p.Arg80= (c.240C>T) is rare (popmax 0.332%, mid) (gnomAD).

CRYGD p.Arg80=

c.240C>T · rs201111017 · VCV1147525

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.332%, mid)

Conditions

Aculeiform 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 -0.053	GERP 0.63, phastCons 0.061
Overall
CADD	14.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.332% Middle Eastern · 15/4,522 alleles

Filtering AF 0.204% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.165%

Overall 0.00875% 141/1,611,690 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.332%	301
South Asian	0.0363%	2,757
Admixed American	0.025%	4,001
Remaining individualsnot grpmax-eligible	0.0128%	7,791
European (non-Finnish)	0.00585%	17,100
African / African-American	0.00133%	74,986

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.Arg80=
Coding: c.240C>T
MANE Select: NM_006891
dbSNP: rs201111017
Type: single nucleotide variant
Location: chr2:208124124 (GRCh38)
Gene constraint: LOEUF 1.796 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.45 · 16 PDB
Residue 80: 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

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

Similar variants

CRYGD p.Arg140Ter Pathogenic ★★ same condition
CRYGD p.Trp157Ter Pathogenic/Likely pathogenic ★★ same condition
CRYGD p.Arg115His Uncertain significance ★★ ⚠ same condition
CRYGD p.Arg140Gln Uncertain significance ★★ ⚠ same condition
CRYGD p.Ser52Trp Uncertain significance ★★ ⚠ same condition
CRYGD c.9+20C>G Benign ★★ same condition
CRYGD c.9+20C>T Benign ★★ same condition
CRYGD p.Leu167= 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-arg80 (accessed [today's date]).

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