Is CRYBB3 p.Ser71= (c.213C>T) pathogenic?

CRYBB3 p.Ser71= (c.213C>T) is classified Conflicting classifications of pathogenicity in CRYBB3 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2023-10-04). Rare (popmax 0.181%, mid); Associated with cataract 22 multiple types.

What condition is associated with CRYBB3 p.Ser71= (c.213C>T)?

CRYBB3 p.Ser71= (c.213C>T) is associated with cataract 22 multiple types (ClinVar).

How common is CRYBB3 p.Ser71= (c.213C>T) in the general population?

CRYBB3 p.Ser71= (c.213C>T) is rare (popmax 0.181%, mid) (gnomAD).

How is Early onset non-syndromic cataract inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CRYBB3 p.Ser71=

c.213C>T · rs201863246 · VCV340952

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.181%, mid)

Conditions

cataract 22 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
Pangolin	Δ0.28	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 0.74	GERP 0.37, phastCons 0.37
Overall
CADD	7.585	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.181% Middle Eastern · 11/6,062 alleles

Filtering AF 0.102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0787%

Overall 0.0031% 50/1,614,178 alleles · rare exomes 43/1,461,880 · genomes 7/152,298 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.181%	551
African / African-American	0.0293%	3,411
Remaining individualsnot grpmax-eligible	0.0048%	20,837
Admixed American	0.00333%	30,009
European (non-Finnish)	0.00102%	98,334

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: CRYBB3
Protein: p.Ser71=
Coding: c.213C>T
MANE Select: NM_004076
dbSNP: rs201863246
Type: single nucleotide variant
Location: chr22:25203781 (GRCh38)
Gene constraint: LOEUF 1.588 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.52 · 1 PDB
Residue 71: a β-strand; the beta/gamma crystallin 'greek key' 2 domain

Full CRYBB3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cataract 22 multiple types — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Early onset non-syndromic cataract (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Infancy, Neonatal

Similar variants

CRYBB3 p.Arg127Cys Uncertain significance ★★ ⚠ same condition
CRYBB3 p.Arg127His Uncertain significance ★★ ⚠ same condition
CRYBB3 p.Arg152Cys Uncertain significance ★★ ⚠ same condition
CRYBB3 p.Arg169Cys Uncertain significance ★★ ⚠ same condition
CRYBB3 p.Arg179His Uncertain significance ★★ ⚠ same condition
CRYBB3 p.Arg207His Uncertain significance ★★ ⚠ same condition
CRYBB3 p.Arg75Cys Uncertain significance ★★ ⚠ same condition
CRYBB3 p.Arg75His 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/crybb3-p-ser71 (accessed [today's date]).

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