Is CRYGD p.Arg37Pro (c.110G>C) pathogenic?

CRYGD p.Arg37Pro (c.110G>C) is classified Likely pathogenic in CRYGD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-24). AlphaMissense: likely pathogenic (0.9663); Absent from gnomAD v4.1; Associated with CRYGD-related disorders.

What condition is associated with CRYGD p.Arg37Pro (c.110G>C)?

CRYGD p.Arg37Pro (c.110G>C) is associated with CRYGD-related disorders (ClinVar).

How common is CRYGD p.Arg37Pro (c.110G>C) in the general population?

CRYGD p.Arg37Pro (c.110G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CRYGD p.Arg37Pro (c.110G>C)?

AlphaMissense predicts likely pathogenic (score 0.9663) — an in-silico prediction, not a clinical call.

CRYGD p.Arg37Pro

c.110G>C · rs1694933681 · VCV2580739

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9663 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CRYGD-related disorders

Computational evidence

Protein change
AlphaMissense	0.9663	likely pathogenic ✓ concordant with ClinVar · top 1% in CRYGD
REVEL	0.788	moderately pathogenic-leaning
SaProt	LLR -16.04	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.4	GERP 2.5, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 2,797 bp · p 0.94 · regional, not allelic
Overall
CADD	25.7	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

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.Arg37Pro
Coding: c.110G>C
MANE Select: NM_006891
dbSNP: rs1694933681
Type: single nucleotide variant
Location: chr2:208124254 (GRCh38)
Gene constraint: LOEUF 1.796 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.45 · 16 PDB
Residue 37: a UniProt-annotated variant site (in ctrct4; very low solubility; crystallizes spontaneously); the beta/gamma crystallin 'greek key' 1 domain; a β-strand

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

Disease context

CRYGD-related disorders

Similar variants

CRYGD p.Arg37Ser Pathogenic ★ same residue
CRYGD p.Arg15Cys Pathogenic ★★ ⚠ same condition
CRYGD p.Pro24Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
CRYGD p.Asn161Ser Uncertain significance ★★ ⚠ same condition
CRYGD p.Cys79Tyr Uncertain significance ★ ⚠ same condition
CRYGD p.Ser75Pro Uncertain significance ★ same condition
CRYGD p.Tyr7His Likely benign same condition
CRYGD p.Tyr93= 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/crygd-p-arg37pro (accessed [today's date]).

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