Is CDX2 p.Arg163Gln (c.488G>A) pathogenic?

CDX2 p.Arg163Gln (c.488G>A) is classified Uncertain significance in CDX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-05). AlphaMissense: ambiguous (0.3957); Very rare (popmax 0.00283%, afr).

How common is CDX2 p.Arg163Gln (c.488G>A) in the general population?

CDX2 p.Arg163Gln (c.488G>A) is very rare (popmax 0.00283%, afr) (gnomAD).

What do computational predictors say about CDX2 p.Arg163Gln (c.488G>A)?

AlphaMissense predicts ambiguous (score 0.3957) — an in-silico prediction, not a clinical call.

CDX2 p.Arg163Gln

c.488G>A · VCV3489801

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3957 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00283%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3957	ambiguous
REVEL	0.117	moderately benign-leaning
SaProt	LLR -7.92	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	GERP 2.1, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 505 bp · p 0.73 · regional, not allelic
Overall
CADD	26.3	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 0.00283% African / African-American · 2/70,652 alleles

Filtering AF 0.00047% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000176%

Overall 0.000192% 3/1,564,372 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00283%	35,326
European (non-Finnish)	8.57e-05%	1,166,434

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.Arg163Gln
Coding: c.488G>A
MANE Select: NM_001265
Type: single nucleotide variant
Location: chr13:27968519 (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.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
CDX2 p.Ala88Ser 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-arg163gln (accessed [today's date]).

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