Is CDX2 p.Cys166Ser (c.496T>A) pathogenic?

CDX2 p.Cys166Ser (c.496T>A) is classified Uncertain significance in CDX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-08). AlphaMissense: likely pathogenic (0.8149); Absent from gnomAD v4.1.

How common is CDX2 p.Cys166Ser (c.496T>A) in the general population?

CDX2 p.Cys166Ser (c.496T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDX2 p.Cys166Ser (c.496T>A)?

AlphaMissense predicts likely pathogenic (score 0.8149) — an in-silico prediction, not a clinical call.

CDX2 p.Cys166Ser

c.496T>A · VCV3999880

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8149 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8149	likely pathogenic
REVEL	0.195	benign-leaning
SaProt	LLR -6.34	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 10	GERP 2.1, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 505 bp · p 0.73 · regional, not allelic
Overall
CADD	22.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDX2
Protein: p.Cys166Ser
Coding: c.496T>A
MANE Select: NM_001265
Type: single nucleotide variant
Location: chr13:27968511 (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-cys166ser (accessed [today's date]).

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