Is CRYBA4 p.Ala79Asp (c.236C>A) pathogenic?

CRYBA4 p.Ala79Asp (c.236C>A) is classified Uncertain significance in CRYBA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-12). AlphaMissense: ambiguous (0.3711); Absent from gnomAD v4.1; Associated with cataract 23.

What condition is associated with CRYBA4 p.Ala79Asp (c.236C>A)?

CRYBA4 p.Ala79Asp (c.236C>A) is associated with cataract 23 (ClinVar).

How common is CRYBA4 p.Ala79Asp (c.236C>A) in the general population?

CRYBA4 p.Ala79Asp (c.236C>A) is absent from gnomAD v4.1 (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.

What do computational predictors say about CRYBA4 p.Ala79Asp (c.236C>A)?

AlphaMissense predicts ambiguous (score 0.3711) — an in-silico prediction, not a clinical call.

CRYBA4 p.Ala79Asp

c.236C>A · VCV4714941

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3711 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

cataract 23

Computational evidence

Protein change
AlphaMissense	0.3711	ambiguous
REVEL	0.483	indeterminate
SaProt	LLR -9.70	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 7,887 bp · p 0.027 · regional, not allelic
Overall
CADD	25.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CRYBA4
Protein: p.Ala79Asp
Coding: c.236C>A
MANE Select: NM_001886
Type: single nucleotide variant
Location: chr22:26625558 (GRCh38)
Gene constraint: LOEUF 1.238 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.64 · 1 PDB
Residue 79: an α-helix; the beta/gamma crystallin 'greek key' 2 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-ala79asp (accessed [today's date]).

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