Is CRB2 p.Ala930Val (c.2789C>T) pathogenic?

CRB2 p.Ala930Val (c.2789C>T) is classified Benign/Likely benign in CRB2 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2025-12-18). AlphaMissense: likely benign (0.0984); Rare (popmax 0.541%, afr); Associated with ventriculomegaly-cystic kidney disease.

What condition is associated with CRB2 p.Ala930Val (c.2789C>T)?

CRB2 p.Ala930Val (c.2789C>T) is associated with ventriculomegaly-cystic kidney disease, focal segmental glomerulosclerosis 9 (ClinVar).

How common is CRB2 p.Ala930Val (c.2789C>T) in the general population?

CRB2 p.Ala930Val (c.2789C>T) is rare (popmax 0.541%, afr) (gnomAD).

How is Ventriculomegaly-cystic kidney disease inherited?

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

What do computational predictors say about CRB2 p.Ala930Val (c.2789C>T)?

AlphaMissense predicts likely benign (score 0.0984) — an in-silico prediction, not a clinical call.

CRB2 p.Ala930Val

c.2789C>T · rs561402183 · VCV736780

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.0984 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.541%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ventriculomegaly-cystic kidney disease

Computational evidence

Protein change
AlphaMissense	0.0984	likely benign
REVEL	0.052	moderately benign-leaning
SaProt	LLR -5.99	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP -2.2	GERP -3.3
Regional constraint	o/e 1.00	unconstrained · MANE · 21 kb · p 0.85 · regional, not allelic
Overall
CADD	1.688	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 0.541% African / African-American · 363/67,080 alleles

Filtering AF 0.495% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.477%

Overall 0.0299% 433/1,450,304 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.541%	185
Admixed American	0.105%	951
Remaining individualsnot grpmax-eligible	0.0412%	2,429
South Asian	0.00682%	14,672
European (non-Finnish)	0.00027%	370,211

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: CRB2
Protein: p.Ala930Val
Coding: c.2789C>T
MANE Select: NM_173689
dbSNP: rs561402183
Type: single nucleotide variant
Location: chr9:123373320 (GRCh38)
Gene constraint: LOEUF 1.202 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.95 · 1 PDB
Residue 930: a UniProt-annotated variant site (in vmckd; uncertain significance); the laminin g-like 3 domain; a UniProt-annotated variant site (in fsgs9; uncertain significance)

Full CRB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ventriculomegaly-cystic kidney disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: focal segmental glomerulosclerosis 9

For Ventriculomegaly-cystic kidney disease (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal

Similar variants

CRB2 p.Arg275Ter Pathogenic ★★ same condition
CRB2 p.Cys105Ter Pathogenic/Likely pathogenic ★★ same condition
CRB2 p.Gly1205Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
CRB2 p.Trp759Ter Pathogenic ★★ same condition
CRB2 p.Ala914Val Uncertain significance ★★ ⚠ same condition
CRB2 p.Arg115Trp Uncertain significance ★★ ⚠ same condition
CRB2 p.Arg466Cys Uncertain significance ★★ ⚠ same condition
CRB2 p.Arg543Trp 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/crb2-p-ala930val (accessed [today's date]).

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