Is CBX6 p.Pro139= (c.417G>T) pathogenic?

CBX6 p.Pro139= (c.417G>T) is classified Likely benign in CBX6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-01). Very rare (popmax 0.00111%, sas).

How common is CBX6 p.Pro139= (c.417G>T) in the general population?

CBX6 p.Pro139= (c.417G>T) is very rare (popmax 0.00111%, sas) (gnomAD).

CBX6 p.Pro139=

c.417G>T · VCV3772217

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00111%, sas)

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 -1.7	GERP -3.8
Overall
CADD	7.333	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00111% South Asian · 1/90,360 alleles

Filtering AF 0.00043% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000686% 11/1,603,710 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00111%	90,360
European (non-Finnish)	0.00085%	117,653

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: CBX6
Protein: p.Pro139=
Coding: c.417G>T
MANE Select: NM_014292
Type: single nucleotide variant
Location: chr22:38867031 (GRCh38)
Gene constraint: LOEUF 0.583 · pLI 0.88 (gnomAD)
Structure: AlphaFold pLDDT 62.15 · 2 PDB
Residue 139: the 'disordered' region

Full CBX6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CBX6 p.Arg72= Benign/Likely benign ★★ same type
CBX6 p.Ala196Val Uncertain significance ★ ⚠ same type
CBX6 p.Ala240Thr Uncertain significance ★ ⚠ same type
CBX6 p.Ala304Asp Uncertain significance ★ ⚠ same type
CBX6 p.Ala304Val Uncertain significance ★ ⚠ same type
CBX6 p.Ala339Val Uncertain significance ★ ⚠ same type
CBX6 p.Ala343Asp Uncertain significance ★ ⚠ same type
CBX6 p.Ala347Thr 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/cbx6-p-pro139 (accessed [today's date]).

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