Is CRYAB p.Thr63Ile (c.188C>T) pathogenic?

CRYAB p.Thr63Ile (c.188C>T) is classified Uncertain significance in CRYAB (ClinVar, Single submitter, 1 submitter; last evaluated 2017-08-23). AlphaMissense: likely pathogenic (0.5792); Absent from gnomAD v4.1.

How common is CRYAB p.Thr63Ile (c.188C>T) in the general population?

CRYAB p.Thr63Ile (c.188C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CRYAB p.Thr63Ile (c.188C>T)?

AlphaMissense predicts likely pathogenic (score 0.5792) — an in-silico prediction, not a clinical call.

CRYAB p.Thr63Ile

c.188C>T · rs782356793 · VCV451483

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5792 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.5792	likely pathogenic
REVEL	0.518	indeterminate
SaProt	LLR -10.87	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 1,286 bp · p 0.3 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Thr63Ile
Coding: c.188C>T
MANE Select: NM_001289808
dbSNP: rs782356793
Type: single nucleotide variant
Location: chr11:111911537 (GRCh38)
Gene constraint: LOEUF 1.18 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.42 · 21 PDB
Residue 63: the shsp domain

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

Similar variants

CRYAB p.Thr63Ala Uncertain significance ★★ ⚠ same residue
CRYAB p.Thr63Asn Uncertain significance ★ ⚠ same residue
CRYAB p.Thr63= Likely benign ★ same residue
CRYAB c.324+4T>A Uncertain significance ★★ same type
CRYAB c.324+5G>T Uncertain significance ★★ same type
CRYAB c.325-1G>A Uncertain significance ★★ same type
CRYAB c.325-2A>G Uncertain significance ★★ same type
CRYAB c.-5C>T Uncertain significance ★★ same type

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-thr63ile (accessed [today's date]).

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