Is CRYBB1 p.Arg90Cys (c.268C>T) pathogenic?

CRYBB1 p.Arg90Cys (c.268C>T) is classified Uncertain significance in CRYBB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-07). AlphaMissense: likely benign (0.1903); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with CRYBB1 p.Arg90Cys (c.268C>T)?

CRYBB1 p.Arg90Cys (c.268C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CRYBB1 p.Arg90Cys (c.268C>T) in the general population?

CRYBB1 p.Arg90Cys (c.268C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CRYBB1 p.Arg90Cys (c.268C>T)?

AlphaMissense predicts likely benign (score 0.1903) — an in-silico prediction, not a clinical call.

CRYBB1 p.Arg90Cys

c.268C>T · VCV3497361

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1903 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.1903	likely benign
REVEL	0.769	pathogenic-leaning
SaProt	LLR -7.16	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.7	GERP -3.9, phastCons 0.009
Regional constraint	o/e 0.86	unconstrained · MANE · 17 kb · p 0.0069 · regional, not allelic
Overall
CADD	23.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,860 alleles

Overall 0.000124% 2/1,613,666 alleles · very rare exomes 2/1,461,566 · genomes 0/152,100 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,860
South Asian	0.0011%	91,062

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CRYBB1
Protein: p.Arg90Cys
Coding: c.268C>T
MANE Select: NM_001887
Type: single nucleotide variant
Location: chr22:26612103 (GRCh38)

Full CRYBB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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/crybb1-p-arg90cys (accessed [today's date]).

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