Is CRYBA1 p.Pro30Leu (c.89C>T) pathogenic?

CRYBA1 p.Pro30Leu (c.89C>T) is classified Benign/Likely benign in CRYBA1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.1101); Rare (popmax 0.798%, afr); Associated with cataract 10 multiple types.

What condition is associated with CRYBA1 p.Pro30Leu (c.89C>T)?

CRYBA1 p.Pro30Leu (c.89C>T) is associated with cataract 10 multiple types (ClinVar).

How common is CRYBA1 p.Pro30Leu (c.89C>T) in the general population?

CRYBA1 p.Pro30Leu (c.89C>T) is rare (popmax 0.798%, 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.

What do computational predictors say about CRYBA1 p.Pro30Leu (c.89C>T)?

AlphaMissense predicts likely benign (score 0.1101) — an in-silico prediction, not a clinical call.

CRYBA1 p.Pro30Leu

c.89C>T · rs144800101 · VCV702784

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1101 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.798%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cataract 10 multiple types

Computational evidence

Protein change
AlphaMissense	0.1101	likely benign
REVEL	0.194	benign-leaning
SaProt	LLR -8.67	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 0.98, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 7,482 bp · p 0.0017 · regional, not allelic
Overall
CADD	18.37	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

Grpmax group 0.798% African / African-American · 598/74,920 alleles

Filtering AF 0.745% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.724%

Overall 0.0389% 626/1,610,626 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.798%	125
Remaining individualsnot grpmax-eligible	0.0257%	3,899
Admixed American	0.02%	5,001

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: CRYBA1
Protein: p.Pro30Leu
Coding: c.89C>T
MANE Select: NM_005208
dbSNP: rs144800101
Type: single nucleotide variant
Location: chr17:29249199 (GRCh38)
Gene constraint: LOEUF 0.987 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.27
Residue 30: the 'n-terminal arm' region

Full CRYBA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cataract 10 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

CRYBA1 c.215+1G>A Pathogenic/Likely pathogenic ★★ same condition
CRYBA1 c.215+1G>T Pathogenic/Likely pathogenic ★★ same condition
CRYBA1 c.500+1G>A Likely pathogenic ★★ same condition
CRYBA1 p.Arg109His Uncertain significance ★★ ⚠ same condition
CRYBA1 p.Glu39Asp Uncertain significance ★★ same condition
CRYBA1 p.Leu183Ter Uncertain significance ★★ same condition
CRYBA1 c.215+16C>T Benign ★★ same condition
CRYBA1 c.97-8C>T 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/cryba1-p-pro30leu (accessed [today's date]).

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