Is CRYAB p.Glu34fs (c.100dup) pathogenic?

CRYAB p.Glu34fs (c.100dup) is classified Likely pathogenic in CRYAB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-22). Absent from gnomAD; Associated with CRYAB-related disorder.

What condition is associated with CRYAB p.Glu34fs (c.100dup)?

CRYAB p.Glu34fs (c.100dup) is associated with CRYAB-related disorder (ClinVar).

How common is CRYAB p.Glu34fs (c.100dup) in the general population?

CRYAB p.Glu34fs (c.100dup) is absent from gnomAD (gnomAD).

CRYAB p.Glu34fs

c.100dup · rs2497884970 · VCV2630615

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

CRYAB-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 3
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	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.Glu34fs
Coding: c.100dup
MANE Select: NM_001289808
dbSNP: rs2497884970
Type: Duplication
Location: chr11:111911624 (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

CRYAB-related disorder

Similar variants

CRYAB p.Glu34Asp Uncertain significance ★★ ⚠ same residue
CRYAB p.Lys174fs Conflicting classifications of pathogenicity ★ same condition
CRYAB p.Tyr122Ter Uncertain significance ★ same condition
CRYAB c.324+13dup Benign/Likely benign ★★ same type
CRYAB c.201+2_201+3dup Uncertain significance ★ same type
CRYAB c.202-9_214dup Uncertain significance ★ same type
CRYAB p.Glu156Ter Uncertain significance ★ same type
CRYAB p.Thr134fs 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-glu34fs (accessed [today's date]).

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