Is CBX2 p.Cys16= (c.48C>T) pathogenic?

CBX2 p.Cys16= (c.48C>T) is classified Likely benign in CBX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-22). Ultra-rare (popmax 0.0224%, nfe).

How common is CBX2 p.Cys16= (c.48C>T) in the general population?

CBX2 p.Cys16= (c.48C>T) is ultra-rare (popmax 0.0224%, nfe) (gnomAD).

CBX2 p.Cys16=

c.48C>T · rs781876862 · VCV2421844

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0224%, nfe)

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 4.3	GERP -0.68, phastCons 1
Overall
CADD	15.89	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0224% European (non-Finnish) · 258/1,152,858 alleles

Filtering AF 0.0201% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0192%

Overall 0.0195% 301/1,546,630 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0432%	2,314
European (non-Finnish)grpmax	0.0224%	4,468
Remaining individualsnot grpmax-eligible	0.0201%	4,988
Admixed American	0.00746%	13,413
South Asian	0.00355%	28,202
Ashkenazi Jewishnot grpmax-eligible	0.00354%	28,212
African / African-American	0.00277%	36,043

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Cys16=
Coding: c.48C>T
MANE Select: NM_005189
dbSNP: rs781876862
Type: single nucleotide variant
Location: chr17:79778283 (GRCh38)
Gene constraint: LOEUF 0.946 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.29 · 3 PDB
Residue 16: the chromo domain; a β-strand; the 'involved in the interaction with h3c15 and h3c1' region

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-cys16 (accessed [today's date]).

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