Is CRYBB2 p.Gln183Ter (c.547C>T) pathogenic?

CRYBB2 p.Gln183Ter (c.547C>T) is classified Uncertain significance in CRYBB2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-23). Absent from gnomAD v4.1; Associated with CRYBB2-related disorder.

What condition is associated with CRYBB2 p.Gln183Ter (c.547C>T)?

CRYBB2 p.Gln183Ter (c.547C>T) is associated with CRYBB2-related disorder (ClinVar).

How common is CRYBB2 p.Gln183Ter (c.547C>T) in the general population?

CRYBB2 p.Gln183Ter (c.547C>T) is absent from gnomAD v4.1 (gnomAD).

CRYBB2 p.Gln183Ter

c.547C>T · rs759396008 · VCV985072

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

CRYBB2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	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 · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.8, phastCons 1
Overall
CADD	44.0	PHRED · no single calibrated threshold — expert panels disagree

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

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: CRYBB2
Protein: p.Gln183Ter
Coding: c.547C>T
MANE Select: NM_000496
dbSNP: rs759396008
Type: single nucleotide variant
Location: chr22:25231701 (GRCh38)
Gene constraint: LOEUF 0.765 · pLI 0.09 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 89.05 · 3 PDB
Residue 183: a UniProt-annotated variant site (in ctrct3); the beta/gamma crystallin 'greek key' 4 domain

Full CRYBB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CRYBB2-related disorder

Similar variants

CRYBB2 p.Gln183Lys Uncertain significance ★ ⚠ same residue
CRYBB2 p.Arg188Cys Pathogenic/Likely pathogenic ★★ same condition
CRYBB2 p.Gln155Ter Pathogenic/Likely pathogenic ★★ same condition
CRYBB2 c.173+5G>A Uncertain significance ★★ same condition
CRYBB2 p.Arg188Pro Likely pathogenic ★ same condition
CRYBB2 p.Tyr154Ter Likely pathogenic ★ same condition
CRYBB2 p.Thr150Arg Uncertain significance ★ ⚠ same condition
CRYBB2 p.Val187Met 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/crybb2-p-gln183ter (accessed [today's date]).

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