Is CBX7 p.Pro195Ala (c.583C>G) pathogenic?

CBX7 p.Pro195Ala (c.583C>G) is classified Uncertain significance in CBX7 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-06). AlphaMissense: likely benign (0.0565); Ultra-rare (popmax 0.01%, amr).

How common is CBX7 p.Pro195Ala (c.583C>G) in the general population?

CBX7 p.Pro195Ala (c.583C>G) is ultra-rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about CBX7 p.Pro195Ala (c.583C>G)?

AlphaMissense predicts likely benign (score 0.0565) — an in-silico prediction, not a clinical call.

CBX7 p.Pro195Ala

c.583C>G · rs772181165 · VCV2253210

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0565 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0565	likely benign
REVEL	0.072	moderately benign-leaning
SaProt	LLR -6.40	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.4	GERP -1.1, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 858 bp · p 0.23 · regional, not allelic
Overall
CADD	16.63	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 0.01% Admixed American · 6/59,858 alleles

Filtering AF 0.00429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00296%

Overall 0.001% 16/1,600,096 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	9,976
European (non-Finnish)	0.000848%	117,929

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.Pro195Ala
Coding: c.583C>G
MANE Select: NM_175709
dbSNP: rs772181165
Type: single nucleotide variant
Location: chr22:39134416 (GRCh38)
Gene constraint: LOEUF 0.767 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 67.01 · 9 PDB
Residue 195: 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-pro195ala (accessed [today's date]).

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