Is CRB2 p.Arg911His (c.2732G>A) pathogenic?

CRB2 p.Arg911His (c.2732G>A) is classified Uncertain significance in CRB2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-05). AlphaMissense: likely benign (0.1347); Ultra-rare (popmax 0.0224%, mid); Associated with Inborn genetic diseases.

What condition is associated with CRB2 p.Arg911His (c.2732G>A)?

CRB2 p.Arg911His (c.2732G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CRB2 p.Arg911His (c.2732G>A) in the general population?

CRB2 p.Arg911His (c.2732G>A) is ultra-rare (popmax 0.0224%, mid) (gnomAD).

What do computational predictors say about CRB2 p.Arg911His (c.2732G>A)?

AlphaMissense predicts likely benign (score 0.1347) — an in-silico prediction, not a clinical call.

CRB2 p.Arg911His

c.2732G>A · rs1007746379 · VCV1908223

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1347 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0224%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1347	likely benign
REVEL	0.301	indeterminate
SaProt	LLR -7.00	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.7	GERP 0.6, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 21 kb · p 0.85 · regional, not allelic
Overall
CADD	24.0	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 0.0224% Middle Eastern · 1/4,460 alleles

Filtering AF 0.00455% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00414%

Overall 0.00451% 67/1,487,116 alleles · ultra-rare exomes 60/1,334,988 · genomes 7/152,128 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0224%	4,460
European (non-Finnish)	0.00567%	17,623
East Asian	0.00282%	35,500
African / African-American	0.00147%	68,070

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.Arg911His
Coding: c.2732G>A
MANE Select: NM_173689
dbSNP: rs1007746379
Type: single nucleotide variant
Location: chr9:123373263 (GRCh38)
Gene constraint: LOEUF 1.202 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.95 · 1 PDB
Residue 911: 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.Arg911Cys 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-arg911his (accessed [today's date]).

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