Is CRYBB2 p.Thr91= (c.273G>A) pathogenic?

CRYBB2 p.Thr91= (c.273G>A) is classified Benign in CRYBB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-02). Rare (popmax 0.399%, afr); Associated with cataract 3 multiple types.

What condition is associated with CRYBB2 p.Thr91= (c.273G>A)?

CRYBB2 p.Thr91= (c.273G>A) is associated with cataract 3 multiple types (ClinVar).

How common is CRYBB2 p.Thr91= (c.273G>A) in the general population?

CRYBB2 p.Thr91= (c.273G>A) is rare (popmax 0.399%, afr) (gnomAD).

CRYBB2 p.Thr91=

c.273G>A · rs146090932 · VCV1933674

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.399%, afr)

Conditions

cataract 3 multiple types

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -10	GERP -3.7
Overall
CADD	1.544	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.399% African / African-American · 299/75,030 alleles

Filtering AF 0.361% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.347%

Overall 0.0216% 348/1,614,116 alleles · rare exomes 183/1,461,874 · genomes 165/152,242 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.399%	251
Remaining individualsnot grpmax-eligible	0.0384%	2,604
Admixed American	0.0117%	8,575
South Asian	0.00659%	15,180
European (non-Finnish)	0.00102%	98,333

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: CRYBB2
Protein: p.Thr91=
Coding: c.273G>A
MANE Select: NM_000496
dbSNP: rs146090932
Type: single nucleotide variant
Location: chr22:25227952 (GRCh38)
Gene constraint: LOEUF 0.765 · pLI 0.09 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 89.05 · 3 PDB
Residue 91: the beta/gamma crystallin 'greek key' 2 domain

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

Disease context

cataract 3 multiple types — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CRYBB2 p.Thr91Met Uncertain significance ★ ⚠ same residue
CRYBB2 p.Arg188Cys Pathogenic/Likely pathogenic ★★ same condition
CRYBB2 p.Arg188His Pathogenic ★★ same condition
CRYBB2 p.Gln155Ter Pathogenic/Likely pathogenic ★★ same condition
CRYBB2 p.Gly119Arg Pathogenic/Likely pathogenic ★★ same condition
CRYBB2 p.Arg160Pro Uncertain significance ★★ ⚠ same condition
CRYBB2 p.Gly57Glu Uncertain significance ★★ ⚠ same condition
CRYBB2 p.Gly61Ser Uncertain significance ★★ ⚠ 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-thr91 (accessed [today's date]).

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