Is CDX1 p.Arg183Trp (c.547C>T) pathogenic?

CDX1 p.Arg183Trp (c.547C>T) is classified Uncertain significance in CDX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-15). AlphaMissense: likely pathogenic (0.9909); Ultra-rare (popmax 0.0112%, eas).

How common is CDX1 p.Arg183Trp (c.547C>T) in the general population?

CDX1 p.Arg183Trp (c.547C>T) is ultra-rare (popmax 0.0112%, eas) (gnomAD).

What do computational predictors say about CDX1 p.Arg183Trp (c.547C>T)?

AlphaMissense predicts likely pathogenic (score 0.9909) — an in-silico prediction, not a clinical call.

CDX1 p.Arg183Trp

c.547C>T · rs140956520 · VCV3141761

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9909 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0112%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9909	likely pathogenic
REVEL	0.882	moderately pathogenic-leaning
SaProt	LLR -13.96	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -3.5, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 17 kb · p 0.73 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0112% East Asian · 5/44,808 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.00273% 44/1,612,898 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.032%	3,121
East Asiangrpmax	0.0112%	8,962
Admixed American	0.00334%	29,919
African / African-American	0.00134%	74,876
European (non-Finnish)	0.00127%	78,634
South Asian	0.0011%	90,914

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CDX1
Protein: p.Arg183Trp
Coding: c.547C>T
MANE Select: NM_001804
dbSNP: rs140956520
Type: single nucleotide variant
Location: chr5:150182869 (GRCh38)
Gene constraint: LOEUF 1.625 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.02 · 2 PDB
Residue 183: a DNA-binding region; an α-helix

Full CDX1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDX1 p.Arg183Gln Uncertain significance ★ ⚠ same residue
CDX1 p.Gly143Arg Uncertain significance ★★ ⚠ same type
CDX1 p.Ala21Val Uncertain significance ★ ⚠ same type
CDX1 p.Ala38Pro Uncertain significance ★ ⚠ same type
CDX1 p.Ala60Val Uncertain significance ★ ⚠ same type
CDX1 p.Ala63Pro Uncertain significance ★ ⚠ same type
CDX1 p.Ala82Val Uncertain significance ★ ⚠ same type
CDX1 p.Arg137Leu 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/cdx1-p-arg183trp (accessed [today's date]).

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