Is CRYBB3 p.Gln78= (c.234G>A) pathogenic?

CRYBB3 p.Gln78= (c.234G>A) is classified Likely benign in CRYBB3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-12). Very rare (popmax 0.00167%, amr); Associated with CRYBB3-related disorder.

What condition is associated with CRYBB3 p.Gln78= (c.234G>A)?

CRYBB3 p.Gln78= (c.234G>A) is associated with CRYBB3-related disorder (ClinVar).

How common is CRYBB3 p.Gln78= (c.234G>A) in the general population?

CRYBB3 p.Gln78= (c.234G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

CRYBB3 p.Gln78=

c.234G>A · rs201028562 · VCV3046411

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

CRYBB3-related disorder

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 1.7	GERP 0.48, phastCons 1
Overall
CADD	5.215	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,026 alleles

Overall 0.000124% 2/1,614,212 alleles · very rare exomes 1/1,461,886 · genomes 1/152,326 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,026
European (non-Finnish)	8.47e-05%	1,180,038

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.Gln78=
Coding: c.234G>A
MANE Select: NM_004076
dbSNP: rs201028562
Type: single nucleotide variant
Location: chr22:25203802 (GRCh38)
Gene constraint: LOEUF 1.588 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.52 · 1 PDB
Residue 78: 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

CRYBB3-related disorder

Similar variants

CRYBB3 p.Glu183Ter Conflicting classifications of pathogenicity ★ same condition
CRYBB3 p.Ala141= Likely benign same condition
CRYBB3 p.Arg127Cys Uncertain significance ★★ ⚠ same type
CRYBB3 p.Arg127His Uncertain significance ★★ ⚠ same type
CRYBB3 p.Arg152Cys Uncertain significance ★★ ⚠ same type
CRYBB3 p.Arg169Cys Uncertain significance ★★ ⚠ same type
CRYBB3 p.Arg179His Uncertain significance ★★ ⚠ same type
CRYBB3 p.Arg196His Uncertain significance ★★ ⚠ 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/crybb3-p-gln78 (accessed [today's date]).

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