Is CBX4 p.Asp102Glu (c.306C>A) pathogenic?

CBX4 p.Asp102Glu (c.306C>A) is classified Uncertain significance in CBX4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-27). AlphaMissense: likely benign (0.1318); Ultra-rare (popmax 0.0986%, afr).

How common is CBX4 p.Asp102Glu (c.306C>A) in the general population?

CBX4 p.Asp102Glu (c.306C>A) is ultra-rare (popmax 0.0986%, afr) (gnomAD).

What do computational predictors say about CBX4 p.Asp102Glu (c.306C>A)?

AlphaMissense predicts likely benign (score 0.1318) — an in-silico prediction, not a clinical call.

CBX4 p.Asp102Glu

c.306C>A · VCV3485716

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1318 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0986%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1318	likely benign
REVEL	0.019	moderately benign-leaning
SaProt	LLR -5.27	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 5	GERP -0.42, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 1,409 bp · p 0.52 · regional, not allelic
Overall
CADD	21.0	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 0.0986% African / African-American · 74/75,046 alleles

Filtering AF 0.0805% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0738%

Overall 0.00508% 82/1,614,160 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0986%	1,014
Remaining individualsnot grpmax-eligible	0.008%	12,502
Admixed American	0.005%	20,010

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: CBX4
Protein: p.Asp102Glu
Coding: c.306C>A
MANE Select: NM_003655
Type: single nucleotide variant
Location: chr17:79835336 (GRCh38)
Gene constraint: LOEUF 0.48 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 55.01 · 3 PDB
Residue 102: the 'interaction with bmi1' region; the 'disordered' region

Full CBX4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CBX4 p.Arg70= Benign ★★ same type
CBX4 p.Ala138Val Uncertain significance ★ ⚠ same type
CBX4 p.Ala236Val Uncertain significance ★ ⚠ same type
CBX4 p.Ala298Val Uncertain significance ★ ⚠ same type
CBX4 p.Ala314Pro Uncertain significance ★ ⚠ same type
CBX4 p.Ala316Ser Uncertain significance ★ ⚠ same type
CBX4 p.Ala316Thr Uncertain significance ★ ⚠ same type
CBX4 p.Ala323Glu 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/cbx4-p-asp102glu (accessed [today's date]).

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