Is CBX2 p.Ser19Arg (c.57C>A) pathogenic?

CBX2 p.Ser19Arg (c.57C>A) is classified Uncertain significance in CBX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-06). AlphaMissense: likely pathogenic (0.9492); Absent from gnomAD v4.1.

How common is CBX2 p.Ser19Arg (c.57C>A) in the general population?

CBX2 p.Ser19Arg (c.57C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CBX2 p.Ser19Arg (c.57C>A)?

AlphaMissense predicts likely pathogenic (score 0.9492) — an in-silico prediction, not a clinical call.

CBX2 p.Ser19Arg

c.57C>A · VCV4220049

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9492 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,552,646)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9492	likely pathogenic
REVEL	0.295	indeterminate
SaProt	LLR -5.78	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.91 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.35	GERP -3.4, phastCons 0.99
Regional constraint	o/e 0.61	unconstrained · MANE · 1,184 bp · p 0.00085 · regional, not allelic
Overall
CADD	24.3	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

No allele count reported in gnomAD v4.1 (AN 1,552,646). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CBX2
Protein: p.Ser19Arg
Coding: c.57C>A
MANE Select: NM_005189
Type: single nucleotide variant
Location: chr17:79778292 (GRCh38)
Gene constraint: LOEUF 0.946 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.29 · 3 PDB
Residue 19: 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-ser19arg (accessed [today's date]).

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