Is CDX2 p.Gln254Pro (c.761A>C) pathogenic?

CDX2 p.Gln254Pro (c.761A>C) is classified Uncertain significance in CDX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-18). AlphaMissense: likely benign (0.0629); Absent from gnomAD v4.1.

How common is CDX2 p.Gln254Pro (c.761A>C) in the general population?

CDX2 p.Gln254Pro (c.761A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDX2 p.Gln254Pro (c.761A>C)?

AlphaMissense predicts likely benign (score 0.0629) — an in-silico prediction, not a clinical call.

CDX2 p.Gln254Pro

c.761A>C · rs1284944894 · VCV2237106

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0629 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0629	likely benign
REVEL	0.182	moderately benign-leaning
SaProt	LLR -12.97	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.82	GERP 1, phastCons 0.89
Regional constraint	o/e 0.51	unconstrained · MANE · 5,235 bp · p 5.8e-08 · regional, not allelic
Overall
CADD	16.78	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.Gln254Pro
Coding: c.761A>C
MANE Select: NM_001265
dbSNP: rs1284944894
Type: single nucleotide variant
Location: chr13:27963296 (GRCh38)
Gene constraint: LOEUF 0.609 · pLI 0.79 (gnomAD)
Structure: AlphaFold pLDDT 63.77 · 4 PDB
Residue 254: an α-helix; the 'disordered' region

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-gln254pro (accessed [today's date]).

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