Is CRB2 p.Asp736= (c.2208C>T) pathogenic?

CRB2 p.Asp736= (c.2208C>T) is classified Likely benign in CRB2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-04). Very rare (popmax 0.00289%, nfe); Associated with CRB2-related disorder.

What condition is associated with CRB2 p.Asp736= (c.2208C>T)?

CRB2 p.Asp736= (c.2208C>T) is associated with CRB2-related disorder (ClinVar).

How common is CRB2 p.Asp736= (c.2208C>T) in the general population?

CRB2 p.Asp736= (c.2208C>T) is very rare (popmax 0.00289%, nfe) (gnomAD).

CRB2 p.Asp736=

c.2208C>T · rs1348716749 · VCV3047146

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00289%, nfe)

Conditions

CRB2-related disorder

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 -1.9	GERP -4
Overall
CADD	3.179	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00289% European (non-Finnish) · 34/1,175,016 alleles

Filtering AF 0.00208% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00184%

Overall 0.00218% 35/1,604,742 alleles · very rare exomes 32/1,452,538 · genomes 3/152,204 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00289%	34,559
Remaining individualsnot grpmax-eligible	0.00161%	62,084

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.Asp736=
Coding: c.2208C>T
MANE Select: NM_173689
dbSNP: rs1348716749
Type: single nucleotide variant
Location: chr9:123371350 (GRCh38)
Gene constraint: LOEUF 1.202 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.95 · 1 PDB
Residue 736: 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

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-asp736 (accessed [today's date]).

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