Is CBR1 p.His265Arg (c.794A>G) pathogenic?

CBR1 p.His265Arg (c.794A>G) is classified Uncertain significance in CBR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-21). AlphaMissense: likely benign (0.2618); Absent from gnomAD v4.1.

How common is CBR1 p.His265Arg (c.794A>G) in the general population?

CBR1 p.His265Arg (c.794A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CBR1 p.His265Arg (c.794A>G)?

AlphaMissense predicts likely benign (score 0.2618) — an in-silico prediction, not a clinical call.

CBR1 p.His265Arg

c.794A>G · rs2065363905 · VCV2338072

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2618 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2618	likely benign
REVEL	0.237	benign-leaning
SaProt	LLR -12.61	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 2,763 bp · p 0.69 · regional, not allelic
Overall
CADD	22.1	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CBR1
Protein: p.His265Arg
Coding: c.794A>G
MANE Select: NM_001757
dbSNP: rs2065363905
Type: single nucleotide variant
Location: chr21:36072842 (GRCh38)
Gene constraint: LOEUF 1.419 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.88 · 6 PDB

Full CBR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CBR1 p.Thr197= Benign ★★ same type
CBR1 p.Ala209Thr Uncertain significance ★ ⚠ same type
CBR1 p.Ala255Val Uncertain significance ★ ⚠ same type
CBR1 p.Ala52Val Uncertain significance ★ ⚠ same type
CBR1 p.Arg119Gln Uncertain significance ★ ⚠ same type
CBR1 p.Arg159Cys Uncertain significance ★ ⚠ same type
CBR1 p.Arg159His Uncertain significance ★ ⚠ same type
CBR1 p.Arg232Lys Uncertain significance ★ ⚠ same type

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/cbr1-p-his265arg (accessed [today's date]).

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