Is CRB2 p.Ser692= (c.2076C>T) pathogenic?

CRB2 p.Ser692= (c.2076C>T) is classified Benign in CRB2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). Common (popmax 30.1%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with ventriculomegaly-cystic kidney disease.

What condition is associated with CRB2 p.Ser692= (c.2076C>T)?

CRB2 p.Ser692= (c.2076C>T) 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.Ser692=

Q: How common is CRB2 p.Ser692= (c.2076C>T) in the general population?

CRB2 p.Ser692= (c.2076C>T) is common (popmax 30.1%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2076C>T · rs13290763 · VCV1167629

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 30.1%, nfe) — 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 -5.3	GERP -4.3
Overall
CADD	0.039	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 30.1% European (non-Finnish) · 354,901/1,179,976 alleles

Filtering AF 30% ClinGen BA1/BS1 input FAF95, joint · FAF99 30%

Overall 27.7% 447,768/1,613,782 alleles · common exomes 413,791/1,461,578 · genomes 33,977/152,204 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	36.3%	3
Amishnot grpmax-eligible	33.6%	3
European (non-Finnish)grpmax	30.1%	3
Middle Eastern	29%	3
Remaining individualsnot grpmax-eligible	27.2%	4
South Asian	24.9%	4
East Asian	24%	4
Finnishnot grpmax-eligible	22.6%	4
Admixed American	16.1%	6
African / African-American	7.36%	14

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser692=
Coding: c.2076C>T
MANE Select: NM_173689
dbSNP: rs13290763
Type: single nucleotide variant
Location: chr9:123371218 (GRCh38)
Gene constraint: LOEUF 1.202 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.95 · 1 PDB
Residue 692: the laminin g-like 2 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-ser692 (accessed [today's date]).

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