Is CRB2 p.Arg934Pro (c.2801G>C) pathogenic?

CRB2 p.Arg934Pro (c.2801G>C) is classified Uncertain significance in CRB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-01). AlphaMissense: likely benign (0.1764); Very rare (popmax 0.000813%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CRB2 p.Arg934Pro (c.2801G>C)?

CRB2 p.Arg934Pro (c.2801G>C) is associated with Inborn genetic diseases (ClinVar).

How common is CRB2 p.Arg934Pro (c.2801G>C) in the general population?

CRB2 p.Arg934Pro (c.2801G>C) is very rare (popmax 0.000813%, nfe) (gnomAD).

What do computational predictors say about CRB2 p.Arg934Pro (c.2801G>C)?

AlphaMissense predicts likely benign (score 0.1764) — an in-silico prediction, not a clinical call.

CRB2 p.Arg934Pro

c.2801G>C · rs1403394228 · VCV2248127

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1764 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000813%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1764	likely benign
REVEL	0.468	indeterminate
SaProt	LLR -9.38	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP -0.35, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 21 kb · p 0.85 · regional, not allelic
Overall
CADD	18.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000813% European (non-Finnish) · 9/1,107,472 alleles

Filtering AF 0.000382% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.000697% 9/1,292,030 alleles · very rare

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.Arg934Pro
Coding: c.2801G>C
MANE Select: NM_173689
dbSNP: rs1403394228
Type: single nucleotide variant
Location: chr9:123373332 (GRCh38)
Gene constraint: LOEUF 1.202 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.95 · 1 PDB
Residue 934: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CRB2 p.Arg934Cys Uncertain significance ★★ ⚠ same residue
CRB2 p.Ala1042Thr Uncertain significance ★★ ⚠ same condition
CRB2 p.Ala1266Pro Uncertain significance ★★ ⚠ same condition
CRB2 p.Ala228Thr Uncertain significance ★★ ⚠ same condition
CRB2 p.Ala26Asp Uncertain significance ★★ ⚠ same condition
CRB2 p.Ala325Val Uncertain significance ★★ ⚠ same condition
CRB2 p.Ala80Thr Uncertain significance ★★ ⚠ same condition
CRB2 p.Ala887Thr 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-arg934pro (accessed [today's date]).

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