Is CRB2 p.Ala1007= (c.3021T>C) pathogenic?

CRB2 p.Ala1007= (c.3021T>C) is classified Benign in CRB2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-03). Common (popmax 22.2%, afr) — too common for a highly-penetrant pathogenic allele; Associated with ventriculomegaly-cystic kidney disease.

What condition is associated with CRB2 p.Ala1007= (c.3021T>C)?

CRB2 p.Ala1007= (c.3021T>C) is associated with ventriculomegaly-cystic kidney disease (ClinVar).

How is Ventriculomegaly-cystic kidney disease inherited?

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

CRB2 p.Ala1007=

Q: How common is CRB2 p.Ala1007= (c.3021T>C) in the general population?

CRB2 p.Ala1007= (c.3021T>C) is common (popmax 22.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3021T>C · rs7848449 · VCV1098728

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 22.2%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

ventriculomegaly-cystic kidney disease

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 -9.2	GERP -3
Overall
CADD	1.536	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 22.2% African / African-American · 15,320/68,996 alleles

Filtering AF 21.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 21.8%

Overall 9.65% 143,113/1,482,736 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	22.2%	5
Ashkenazi Jewishnot grpmax-eligible	15.7%	6
Middle Eastern	14.2%	7
South Asian	13.8%	7
Admixed American	13%	8
Remaining individualsnot grpmax-eligible	10.6%	9
Amishnot grpmax-eligible	9.01%	11
European (non-Finnish)	8.44%	12
Finnishnot grpmax-eligible	8.16%	12
East Asian	5.47%	18

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.Ala1007=
Coding: c.3021T>C
MANE Select: NM_173689
dbSNP: rs7848449
Type: single nucleotide variant
Location: chr9:123373552 (GRCh38)
Gene constraint: LOEUF 1.202 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.95 · 1 PDB
Residue 1007: 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

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.Trp759Ter Pathogenic ★★ same condition
CRB2 p.Arg115Trp Uncertain significance ★★ ⚠ same condition
CRB2 p.Gly332Arg Uncertain significance ★★ ⚠ same condition
CRB2 p.Gly941Ser Uncertain significance ★★ ⚠ same condition
CRB2 p.Val824Ile Uncertain significance ★★ ⚠ same condition
CRB2 c.3389+48A>G 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/crb2-p-ala1007 (accessed [today's date]).

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