Is CDX2 p.Ser283Arg (c.849T>A) pathogenic?

CDX2 p.Ser283Arg (c.849T>A) is classified Uncertain significance in CDX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-29). AlphaMissense: likely pathogenic (0.932); Ultra-rare (popmax 0.0517%, amr).

How common is CDX2 p.Ser283Arg (c.849T>A) in the general population?

CDX2 p.Ser283Arg (c.849T>A) is ultra-rare (popmax 0.0517%, amr) (gnomAD).

What do computational predictors say about CDX2 p.Ser283Arg (c.849T>A)?

AlphaMissense predicts likely pathogenic (score 0.932) — an in-silico prediction, not a clinical call.

CDX2 p.Ser283Arg

c.849T>A · rs139907356 · VCV2365383

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.932 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0517%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.932	likely pathogenic
REVEL	0.534	indeterminate
SaProt	LLR -9.48	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.2	GERP -0.25, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 146 bp · p 0.86 · regional, not allelic
Overall
CADD	19.51	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 0.0517% Admixed American · 31/59,998 alleles

Filtering AF 0.0374% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0325%

Overall 0.0044% 71/1,614,034 alleles · ultra-rare exomes 33/1,461,882 · genomes 38/152,152 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0517%	1,935
African / African-American	0.0374%	2,675
Remaining individualsnot grpmax-eligible	0.0192%	5,207

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.Ser283Arg
Coding: c.849T>A
MANE Select: NM_001265
dbSNP: rs139907356
Type: single nucleotide variant
Location: chr13:27963208 (GRCh38)
Gene constraint: LOEUF 0.609 · pLI 0.79 (gnomAD)
Structure: AlphaFold pLDDT 63.77 · 4 PDB
Residue 283: the 'disordered' region; a modified residue (phosphoserine)

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-ser283arg (accessed [today's date]).

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