CRYGD p.Arg140Ter
c.418C>T · rs1337897299 · VCV574060
Pathogenic
Multiple submitters
Classification
Pathogenic
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
2
Aculeiform cataract
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function |
|---|---|---|
| NMD | escapes | premature termination codon in the last exon (3 of 3) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.38 | GERP -1.5 |
| Overall | ||
| CADD | 36.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- CRYGD
- Protein
- p.Arg140Ter
- Coding
- c.418C>T
- MANE Select
- NM_006891
- dbSNP
- rs1337897299
- Type
- single nucleotide variant
- Location
- chr2:208121780 (GRCh38)
- Gene constraint
- LOEUF 1.796 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 96.45 · 16 PDB
- Residue 140
- a UniProt-annotated variant site (in ctrct4; uncertain significance); a UniProt-annotated variant site (in ctrct4); a β-strand; the beta/gamma crystallin 'greek key' 4 domain
Similar variants
- CRYGD p.Arg140Gln Uncertain significance ★★ ⚠ same residue
- CRYGD p.Arg15Cys Pathogenic ★★ ⚠ same condition
- CRYGD p.Pro24Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
- CRYGD p.Trp157Ter Pathogenic/Likely pathogenic ★★ same condition
- CRYGD p.Arg115His Uncertain significance ★★ ⚠ same condition
- CRYGD p.Asn161Ser Uncertain significance ★★ ⚠ same condition
- CRYGD p.Ser52Trp Uncertain significance ★★ ⚠ same condition
- CRYGD c.10-7C>G 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-arg140ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown