Is CRYAB p.Pro20Ser (c.58C>T) pathogenic?

CRYAB p.Pro20Ser (c.58C>T) is classified Pathogenic in CRYAB (ClinVar, No assertion criteria, 1 submitter; last evaluated 2006-08-01). AlphaMissense: likely benign (0.1664); Absent from gnomAD v4.1; Associated with cataract 16 multiple types.

What condition is associated with CRYAB p.Pro20Ser (c.58C>T)?

CRYAB p.Pro20Ser (c.58C>T) is associated with cataract 16 multiple types (ClinVar).

How common is CRYAB p.Pro20Ser (c.58C>T) in the general population?

CRYAB p.Pro20Ser (c.58C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CRYAB p.Pro20Ser (c.58C>T)?

AlphaMissense predicts likely benign (score 0.1664) — an in-silico prediction, not a clinical call.

CRYAB p.Pro20Ser

c.58C>T · rs387907337 · VCV41928

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1664 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cataract 16 multiple types

Computational evidence

Protein change
AlphaMissense	0.1664	likely benign ⚠ discordant with ClinVar
REVEL	0.723	pathogenic-leaning
SaProt	LLR -6.28	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 2.3, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 1,286 bp · p 0.3 · regional, not allelic
Overall
CADD	28.0	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: CRYAB
Protein: p.Pro20Ser
Coding: c.58C>T
MANE Select: NM_001289808
dbSNP: rs387907337
Type: single nucleotide variant
Location: chr11:111911667 (GRCh38)
Gene constraint: LOEUF 1.18 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.42 · 21 PDB

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

Disease context

cataract 16 multiple types — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CRYAB p.Pro20Arg Pathogenic ★ ⚠ same residue
CRYAB p.Pro20= Likely benign ★ same residue
CRYAB p.Ala4Thr Uncertain significance ★★ ⚠ same condition
CRYAB p.Arg107Cys Uncertain significance ★★ ⚠ same condition
CRYAB p.Arg11Gly Uncertain significance ★★ ⚠ same condition
CRYAB p.Arg123Trp Uncertain significance ★★ ⚠ same condition
CRYAB p.Arg157His Uncertain significance ★★ ⚠ same condition
CRYAB p.Arg22His Uncertain significance ★★ ⚠ 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/cryab-p-pro20ser (accessed [today's date]).

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