Is CRYBA1 p.Arg196fs (c.588_591del) pathogenic?

CRYBA1 p.Arg196fs (c.588591del) is classified Likely pathogenic in CRYBA1 (ClinVar, Single submitter, 1 submitter). Absent from gnomAD.

How common is CRYBA1 p.Arg196fs (c.588_591del) in the general population?

CRYBA1 p.Arg196fs (c.588_591del) is absent from gnomAD (gnomAD).

CRYBA1 p.Arg196fs

c.588_591del · rs786205628 · VCV191293

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

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 (6 of 6) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 0.72, 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: CRYBA1
Protein: p.Arg196fs
Coding: c.588_591del
MANE Select: NM_005208
dbSNP: rs786205628
Type: Microsatellite
Location: chr17:29254286 (GRCh38)
Gene constraint: LOEUF 0.987 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.27
Residue 196: the beta/gamma crystallin 'greek key' 4 domain

Full CRYBA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CRYBA1 p.Gly91del Pathogenic/Likely pathogenic ★★ same type
CRYBA1 p.Glu197fs Conflicting classifications of pathogenicity ★ 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/cryba1-p-arg196fs (accessed [today's date]).

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