Is CRYBA4 p.Phe115= (c.345C>T) pathogenic?

CRYBA4 p.Phe115= (c.345C>T) is classified Benign in CRYBA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-26). Rare (popmax 0.209%, afr); Associated with cataract 23.

What condition is associated with CRYBA4 p.Phe115= (c.345C>T)?

CRYBA4 p.Phe115= (c.345C>T) is associated with cataract 23 (ClinVar).

How common is CRYBA4 p.Phe115= (c.345C>T) in the general population?

CRYBA4 p.Phe115= (c.345C>T) is rare (popmax 0.209%, afr) (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.

CRYBA4 p.Phe115=

c.345C>T · rs143888002 · VCV2776090

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.209%, afr)

Conditions

cataract 23

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 0.11	GERP -0.35, phastCons 0.96
Overall
CADD	9.115	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.209% African / African-American · 157/74,976 alleles

Filtering AF 0.183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.172%

Overall 0.0102% 164/1,613,946 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.209%	478
Remaining individualsnot grpmax-eligible	0.008%	12,500
Admixed American	0.00333%	29,992

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: CRYBA4
Protein: p.Phe115=
Coding: c.345C>T
MANE Select: NM_001886
dbSNP: rs143888002
Type: single nucleotide variant
Location: chr22:26628332 (GRCh38)
Gene constraint: LOEUF 1.238 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.64 · 1 PDB
Residue 115: the beta/gamma crystallin 'greek key' 3 domain

Full CRYBA4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cataract 23 — 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

CRYBA4 p.Phe22Ser Uncertain significance ★★ ⚠ same condition
CRYBA4 p.Phe57Val Uncertain significance ★★ ⚠ same condition
CRYBA4 c.159-20A>G Benign ★★ same condition
CRYBA4 c.300+3A>G Benign ★★ same condition
CRYBA4 c.40-1G>C Benign/Likely benign ★★ same condition
CRYBA4 c.444-18G>A Benign ★★ same condition
CRYBA4 p.Arg103Cys Benign/Likely benign ★★ same condition
CRYBA4 p.Gly72= Benign/Likely benign ★★ 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/cryba4-p-phe115 (accessed [today's date]).

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