Is CBX3 p.Arg38Gln (c.113G>A) pathogenic?

CBX3 p.Arg38Gln (c.113G>A) is classified Uncertain significance in CBX3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-03). AlphaMissense: likely pathogenic (0.6004); Very rare (popmax 0.00223%, eas).

How common is CBX3 p.Arg38Gln (c.113G>A) in the general population?

CBX3 p.Arg38Gln (c.113G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CBX3 p.Arg38Gln (c.113G>A)?

AlphaMissense predicts likely pathogenic (score 0.6004) — an in-silico prediction, not a clinical call.

CBX3 p.Arg38Gln

c.113G>A · rs1784678853 · VCV3138057

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6004 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6004	likely pathogenic
REVEL	0.472	indeterminate
SaProt	LLR -13.22	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.9, phastCons 1
Regional constraint	o/e 0.38	unconstrained · MANE · 5,712 bp · p 1.2e-14 · regional, not allelic
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00223% East Asian · 1/44,862 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00041% 6/1,461,634 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,862
European (non-Finnish)	0.000424%	235,977

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: CBX3
Protein: p.Arg38Gln
Coding: c.113G>A
MANE Select: NM_016587
dbSNP: rs1784678853
Type: single nucleotide variant
Location: chr7:26206456 (GRCh38)
Gene constraint: LOEUF 0.565 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 75.94 · 8 PDB
Residue 38: the chromo 1 domain; a β-strand

Full CBX3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CBX3 p.Arg38Leu Uncertain significance ★ ⚠ same residue
CBX3 p.Ala25Thr Uncertain significance ★ ⚠ same type
CBX3 p.Asn4Ser Uncertain significance ★ ⚠ same type
CBX3 p.Gly88Ser Uncertain significance ★ ⚠ same type
CBX3 p.Thr7Ile Uncertain significance ★ ⚠ same type
CBX3 p.Val22Ile Uncertain significance ★ ⚠ same type
CBX3 p.Val40Ala Uncertain significance ★ ⚠ same type
CBX3 c.330+3A>G 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/cbx3-p-arg38gln (accessed [today's date]).

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