Is CRYAB p.Ser59= (c.177C>T) pathogenic?

CRYAB p.Ser59= (c.177C>T) is classified Likely benign in CRYAB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-27). Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with CRYAB p.Ser59= (c.177C>T)?

CRYAB p.Ser59= (c.177C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is CRYAB p.Ser59= (c.177C>T) in the general population?

CRYAB p.Ser59= (c.177C>T) is absent from gnomAD v4.1 (gnomAD).

CRYAB p.Ser59=

c.177C>T · rs1965454125 · VCV1779945

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Overall
CADD	14.52	PHRED · no single calibrated threshold — expert panels disagree

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.Ser59=
Coding: c.177C>T
MANE Select: NM_001289808
dbSNP: rs1965454125
Type: single nucleotide variant
Location: chr11:111911548 (GRCh38)
Gene constraint: LOEUF 1.18 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.42 · 21 PDB
Residue 59: the shsp domain; a modified residue (phosphoserine)

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 p.Ser59Asn Uncertain significance ★ ⚠ same residue
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

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-ser59 (accessed [today's date]).

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