Is CRYAB p.Pro167fs (c.499_505del) pathogenic?

CRYAB p.Pro167fs (c.499505del) is classified Uncertain significance in CRYAB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-27). Absent from gnomAD; Associated with dilated cardiomyopathy 1II.

What condition is associated with CRYAB p.Pro167fs (c.499_505del)?

CRYAB p.Pro167fs (c.499_505del) is associated with dilated cardiomyopathy 1II (ClinVar).

How common is CRYAB p.Pro167fs (c.499_505del) in the general population?

CRYAB p.Pro167fs (c.499_505del) is absent from gnomAD (gnomAD).

How is Familial isolated dilated cardiomyopathy inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CRYAB p.Pro167fs

c.499_505del · rs2497874678 · VCV2022473

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

dilated cardiomyopathy 1II

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (3 of 3) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.3, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CRYAB
Protein: p.Pro167fs
Coding: c.499_505del
MANE Select: NM_001289808
dbSNP: rs2497874678
Type: Deletion
Location: chr11:111908787 (GRCh38)
Gene constraint: LOEUF 1.18 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.42 · 21 PDB
Residue 167: the 'disordered' region

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

Disease context

dilated cardiomyopathy 1II — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial isolated dilated cardiomyopathy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: All ages
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

CRYAB p.Pro167Ala Uncertain significance ★ ⚠ same residue
CRYAB p.Lys82_His83delinsAsn Uncertain significance ★★ same condition
CRYAB p.Arg11fs Pathogenic ★ same condition
CRYAB p.Leu49fs Pathogenic ★ same condition
CRYAB p.Ala126fs Uncertain significance ★ same condition
CRYAB p.Arg50_Phe54del Uncertain significance ★ same condition
CRYAB p.Pro155fs Uncertain significance ★ same condition
CRYAB p.Ser115fs Conflicting classifications of pathogenicity ★ 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-pro167fs (accessed [today's date]).

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