Is CRYAB p.Pro52Leu (c.155C>T) pathogenic?

CRYAB p.Pro52Leu (c.155C>T) is classified Uncertain significance in CRYAB (ClinVar, Single submitter, 1 submitter; last evaluated 2026-06-14). AlphaMissense: likely benign (0.1276); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with CRYAB p.Pro52Leu (c.155C>T)?

CRYAB p.Pro52Leu (c.155C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is CRYAB p.Pro52Leu (c.155C>T) in the general population?

CRYAB p.Pro52Leu (c.155C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CRYAB p.Pro52Leu (c.155C>T)?

AlphaMissense predicts likely benign (score 0.1276) — an in-silico prediction, not a clinical call.

CRYAB p.Pro52Leu

c.155C>T · VCV4869432

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1276 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.1276	likely benign
REVEL	0.531	indeterminate
SaProt	LLR -6.40	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 1,286 bp · p 0.3 · regional, not allelic
Overall
CADD	24.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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.Pro52Leu
Coding: c.155C>T
MANE Select: NM_001289808
Type: single nucleotide variant
Location: chr11:111911570 (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

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CRYAB c.324+4T>A Uncertain significance ★★ same condition
CRYAB c.325-2A>G Uncertain significance ★★ same condition
CRYAB c.-5C>T Uncertain significance ★★ same condition
CRYAB p.Ala171Thr Uncertain significance ★★ ⚠ same condition
CRYAB p.Arg11Cys Uncertain significance ★★ ⚠ same condition
CRYAB p.Arg123Gln Uncertain significance ★★ ⚠ same condition
CRYAB p.Arg157Cys Uncertain significance ★★ ⚠ same condition
CRYAB p.Arg163His 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-pro52leu (accessed [today's date]).

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