Is CRB2 p.Ala899= (c.2697C>T) pathogenic?

CRB2 p.Ala899= (c.2697C>T) is classified Likely benign in CRB2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-08-12). Very rare (popmax 0.00123%, sas); Associated with CRB2-related disorder.

What condition is associated with CRB2 p.Ala899= (c.2697C>T)?

CRB2 p.Ala899= (c.2697C>T) is associated with CRB2-related disorder (ClinVar).

How common is CRB2 p.Ala899= (c.2697C>T) in the general population?

CRB2 p.Ala899= (c.2697C>T) is very rare (popmax 0.00123%, sas) (gnomAD).

CRB2 p.Ala899=

c.2697C>T · VCV3348867

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00123%, sas)

Conditions

CRB2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Overall
CADD	10.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00123% South Asian · 1/81,610 alleles

Overall 0.000133% 2/1,507,366 alleles · very rare exomes 2/1,355,036 · genomes 0/152,330 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00123%	81,610
European (non-Finnish)	8.81e-05%	1,135,302

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.Ala899=
Coding: c.2697C>T
MANE Select: NM_173689
Type: single nucleotide variant
Location: chr9:123373228 (GRCh38)
Gene constraint: LOEUF 1.202 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.95 · 1 PDB
Residue 899: 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

CRB2-related disorder

Similar variants

CRB2 p.Arg1128Cys Uncertain significance ★★ same condition
CRB2 p.Asp594Gly Uncertain significance ★★ ⚠ same condition
CRB2 p.Gln851Ter Likely pathogenic ★ same condition
CRB2 p.Trp976Ter Likely pathogenic ★ same condition
CRB2 p.Arg1115Cys Likely pathogenic ⚠ same condition
CRB2 p.Arg903Cys Uncertain significance ⚠ same condition
CRB2 p.Glu356Lys Uncertain significance ⚠ same condition
CRB2 p.His885Tyr 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-ala899 (accessed [today's date]).

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