Is CBX2 p.Cys89= (c.267C>T) pathogenic?

CBX2 p.Cys89= (c.267C>T) is classified Likely benign in CBX2 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-06-12). Ultra-rare (popmax 0.0267%, amr).

How common is CBX2 p.Cys89= (c.267C>T) in the general population?

CBX2 p.Cys89= (c.267C>T) is ultra-rare (popmax 0.0267%, amr) (gnomAD).

CBX2 p.Cys89=

c.267C>T · rs1328403947 · VCV3043499

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, 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 -2.1	GERP -3.1
Overall
CADD	1.943	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0267% Admixed American · 16/60,012 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00105% 17/1,614,020 alleles · ultra-rare exomes 15/1,461,808 · genomes 2/152,212 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0267%	3,751
South Asian	0.0011%	91,092

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.Cys89=
Coding: c.267C>T
MANE Select: NM_005189
dbSNP: rs1328403947
Type: single nucleotide variant
Location: chr17:79781780 (GRCh38)
Gene constraint: LOEUF 0.946 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.29 · 3 PDB
Residue 89: the 'disordered' region

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

Similar variants

CBX2 p.Cys89fs Uncertain significance ★ same residue
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

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-cys89 (accessed [today's date]).

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