Is CBX2 p.Pro366= (c.1098C>T) pathogenic?

CBX2 p.Pro366= (c.1098C>T) is classified Likely benign in CBX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-06-17). Ultra-rare (popmax 0.095%, amr).

How common is CBX2 p.Pro366= (c.1098C>T) in the general population?

CBX2 p.Pro366= (c.1098C>T) is ultra-rare (popmax 0.095%, amr) (gnomAD).

CBX2 p.Pro366=

c.1098C>T · rs146970180 · VCV749846

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.095%, amr)

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 -7.3	GERP -3.6
Overall
CADD	2.301	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.095% Admixed American · 57/60,012 alleles

Filtering AF 0.0752% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0681%

Overall 0.00595% 96/1,612,566 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.095%	1,053
European (non-Finnish)	0.00322%	31,051
Remaining individualsnot grpmax-eligible	0.0016%	62,456

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: CBX2
Protein: p.Pro366=
Coding: c.1098C>T
MANE Select: NM_005189
dbSNP: rs146970180
Type: single nucleotide variant
Location: chr17:79784541 (GRCh38)
Gene constraint: LOEUF 0.946 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.29 · 3 PDB

Full CBX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CBX2 c.288+52G>T Uncertain significance ★★ same type
CBX2 p.Arg137His Uncertain significance ★★ ⚠ same type
CBX2 p.Gln349His Uncertain significance ★★ ⚠ same type
CBX2 p.Gly133Ser Uncertain significance ★★ ⚠ same type
CBX2 p.Gly287Arg Uncertain significance ★★ ⚠ same type
CBX2 p.Gly332Asp Uncertain significance ★★ ⚠ same type
CBX2 p.Met260Val Uncertain significance ★★ ⚠ same type
CBX2 p.Met404Leu 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/cbx2-p-pro366 (accessed [today's date]).

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