Is CDX2 p.Ter314Arg (c.940T>C) pathogenic?

CDX2 p.Ter314Arg (c.940T>C) is classified Likely pathogenic in CDX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-02-12). Absent from gnomAD v4.1; Associated with sirenomelia.

What condition is associated with CDX2 p.Ter314Arg (c.940T>C)?

CDX2 p.Ter314Arg (c.940T>C) is associated with sirenomelia (ClinVar).

How common is CDX2 p.Ter314Arg (c.940T>C) in the general population?

CDX2 p.Ter314Arg (c.940T>C) is absent from gnomAD v4.1 (gnomAD).

CDX2 p.Ter314Arg

c.940T>C · rs1593181774 · VCV812557

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

sirenomelia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Overall
CADD	18.31	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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.Ter314Arg
Coding: c.940T>C
MANE Select: NM_001265
dbSNP: rs1593181774
Type: single nucleotide variant
Location: chr13:27963117 (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

Disease context

sirenomelia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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
CDX2 p.Arg163Gln 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-ter314arg (accessed [today's date]).

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