Is CBX7 p.Pro213Ser (c.637C>T) pathogenic?

CBX7 p.Pro213Ser (c.637C>T) is classified Uncertain significance in CBX7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-01). AlphaMissense: likely benign (0.222); Very rare (popmax 6.85e-05%).

How common is CBX7 p.Pro213Ser (c.637C>T) in the general population?

CBX7 p.Pro213Ser (c.637C>T) is very rare (popmax 6.85e-05%) (gnomAD).

What do computational predictors say about CBX7 p.Pro213Ser (c.637C>T)?

AlphaMissense predicts likely benign (score 0.222) — an in-silico prediction, not a clinical call.

CBX7 p.Pro213Ser

c.637C>T · VCV3996195

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.222 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.85e-05%)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.222	likely benign
REVEL	0.39	indeterminate
SaProt	LLR -9.79	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.5, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 858 bp · p 0.23 · regional, not allelic
Overall
CADD	27.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.85e-05%

Overall 6.85e-05% 1/1,459,296 alleles · very rare

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: CBX7
Protein: p.Pro213Ser
Coding: c.637C>T
MANE Select: NM_175709
Type: single nucleotide variant
Location: chr22:39134010 (GRCh38)
Gene constraint: LOEUF 0.767 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 67.01 · 9 PDB
Residue 213: the 'disordered' region

Full CBX7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CBX7 p.Ala179Ser Uncertain significance ★ ⚠ same type
CBX7 p.Ala185Val Uncertain significance ★ ⚠ same type
CBX7 p.Ala202Val Uncertain significance ★ ⚠ same type
CBX7 p.Ala214Pro Uncertain significance ★ ⚠ same type
CBX7 p.Ala214Val Uncertain significance ★ ⚠ same type
CBX7 p.Arg140Cys Uncertain significance ★ ⚠ same type
CBX7 p.Arg159Cys Uncertain significance ★ ⚠ same type
CBX7 p.Arg170Gln 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/cbx7-p-pro213ser (accessed [today's date]).

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