Is CDX2 p.Gln36Arg (c.107A>G) pathogenic?

CDX2 p.Gln36Arg (c.107A>G) is classified Uncertain significance in CDX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-06). AlphaMissense: likely pathogenic (0.6416); Very rare (popmax 0.00336%, amr).

How common is CDX2 p.Gln36Arg (c.107A>G) in the general population?

CDX2 p.Gln36Arg (c.107A>G) is very rare (popmax 0.00336%, amr) (gnomAD).

What do computational predictors say about CDX2 p.Gln36Arg (c.107A>G)?

AlphaMissense predicts likely pathogenic (score 0.6416) — an in-silico prediction, not a clinical call.

CDX2 p.Gln36Arg

c.107A>G · rs1213138909 · VCV2473964

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6416 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00336%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6416	likely pathogenic
REVEL	0.274	benign-leaning
SaProt	LLR -5.66	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.9, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 505 bp · p 0.73 · regional, not allelic
Overall
CADD	27.5	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00336% Admixed American · 2/59,510 alleles

Filtering AF 0.000557% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000209%

Overall 0.000412% 6/1,455,468 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00336%	29,755
Remaining individualsnot grpmax-eligible	0.00161%	62,242
European (non-Finnish)	0.000255%	392,795

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: CDX2
Protein: p.Gln36Arg
Coding: c.107A>G
MANE Select: NM_001265
dbSNP: rs1213138909
Type: single nucleotide variant
Location: chr13:27968900 (GRCh38)
Gene constraint: LOEUF 0.609 · pLI 0.79 (gnomAD)
Structure: AlphaFold pLDDT 63.77 · 4 PDB

Full CDX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDX2 p.Gln36Glu Uncertain significance ★ ⚠ same residue
CDX2 p.Ter314Arg Likely pathogenic ★ same type
CDX2 p.Ala103Ser Uncertain significance ★ ⚠ same type
CDX2 p.Ala127Asp Uncertain significance ★ ⚠ same type
CDX2 p.Ala148Ser Uncertain significance ★ ⚠ same type
CDX2 p.Ala46Glu Uncertain significance ★ ⚠ same type
CDX2 p.Ala68Gly Uncertain significance ★ ⚠ same type
CDX2 p.Ala86Ser 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/cdx2-p-gln36arg (accessed [today's date]).

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