Is CRYGD p.Pro24Ser (c.70C>T) pathogenic?

CRYGD p.Pro24Ser (c.70C>T) is classified Pathogenic in CRYGD (ClinVar, No assertion criteria, 1 submitter; last evaluated 2007-09-01). AlphaMissense: likely benign (0.0897); Absent from gnomAD v4.1; Associated with cataract 4 multiple types.

What condition is associated with CRYGD p.Pro24Ser (c.70C>T)?

CRYGD p.Pro24Ser (c.70C>T) is associated with cataract 4 multiple types (ClinVar).

How common is CRYGD p.Pro24Ser (c.70C>T) in the general population?

CRYGD p.Pro24Ser (c.70C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CRYGD p.Pro24Ser (c.70C>T)?

AlphaMissense predicts likely benign (score 0.0897) — an in-silico prediction, not a clinical call.

CRYGD p.Pro24Ser

c.70C>T · rs28931605 · VCV16942

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0897 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

cataract 4 multiple types

Computational evidence

Protein change
AlphaMissense	0.0897	likely benign ⚠ discordant with ClinVar
REVEL	0.402	indeterminate
SaProt	LLR -5.56	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -15	GERP -5
Regional constraint	o/e 1.00	unconstrained · MANE · 2,797 bp · p 0.94 · regional, not allelic
Overall
CADD	0.14	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.Pro24Ser
Coding: c.70C>T
MANE Select: NM_006891
dbSNP: rs28931605
Type: single nucleotide variant
Location: chr2:208124294 (GRCh38)
Gene constraint: LOEUF 1.796 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.45 · 16 PDB
Residue 24: the beta/gamma crystallin 'greek key' 1 domain; a UniProt-annotated variant site (in ctrct4; reduces solubility); a UniProt-annotated variant site (in ctrct4; uncertain significance; reduces solubility)

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

Disease context

cataract 4 multiple types — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CRYGD p.Pro24Thr Pathogenic/Likely pathogenic ★★ ⚠ same residue
CRYGD p.Arg140Ter Pathogenic ★★ same condition
CRYGD p.Arg15Cys Pathogenic ★★ ⚠ same condition
CRYGD p.Asn161Ser Uncertain significance ★★ ⚠ same condition
CRYGD c.10-7C>G Benign ★★ same condition
CRYGD c.252+10T>A Benign/Likely benign ★★ same condition
CRYGD c.252+7A>G Benign ★★ same condition
CRYGD c.-40C>T 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-pro24ser (accessed [today's date]).

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