Is CRYGD p.Ser52Pro (c.154T>C) pathogenic?

CRYGD p.Ser52Pro (c.154T>C) is classified Likely pathogenic in CRYGD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-21). AlphaMissense: ambiguous (0.5526); Absent from gnomAD v4.1; Associated with Aculeiform cataract.

What condition is associated with CRYGD p.Ser52Pro (c.154T>C)?

CRYGD p.Ser52Pro (c.154T>C) is associated with Aculeiform cataract (ClinVar).

How common is CRYGD p.Ser52Pro (c.154T>C) in the general population?

CRYGD p.Ser52Pro (c.154T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CRYGD p.Ser52Pro (c.154T>C)?

AlphaMissense predicts ambiguous (score 0.5526) — an in-silico prediction, not a clinical call.

CRYGD p.Ser52Pro

c.154T>C · rs2469111254 · VCV1994732

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5526 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Aculeiform cataract

Computational evidence

Protein change
AlphaMissense	0.5526	ambiguous
REVEL	0.288	benign-leaning
SaProt	LLR -6.83	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.6	GERP -5
Regional constraint	o/e 1.00	unconstrained · MANE · 2,797 bp · p 0.94 · regional, not allelic
Overall
CADD	3.495	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.Ser52Pro
Coding: c.154T>C
MANE Select: NM_006891
dbSNP: rs2469111254
Type: single nucleotide variant
Location: chr2:208124210 (GRCh38)
Gene constraint: LOEUF 1.796 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.45 · 16 PDB
Residue 52: 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.Ser52Trp Uncertain significance ★★ ⚠ same residue
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 c.9+20C>G Benign ★★ same condition
CRYGD c.9+20C>T Benign ★★ same condition
CRYGD p.Arg80= 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-ser52pro (accessed [today's date]).

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