Is CDX4 p.Pro67Gln (c.200C>A) pathogenic?

CDX4 p.Pro67Gln (c.200C>A) is classified Likely benign in CDX4 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-03-29). AlphaMissense: likely benign (0.08); Rare (popmax 0.331%, nfe).

How common is CDX4 p.Pro67Gln (c.200C>A) in the general population?

CDX4 p.Pro67Gln (c.200C>A) is rare (popmax 0.331%, nfe) (gnomAD).

What do computational predictors say about CDX4 p.Pro67Gln (c.200C>A)?

AlphaMissense predicts likely benign (score 0.08) — an in-silico prediction, not a clinical call.

CDX4 p.Pro67Gln

c.200C>A · rs145092385 · VCV710287

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.08 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.331%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.08	likely benign
REVEL	0.08	moderately benign-leaning
SaProt	LLR -6.93	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.13	GERP 0.17
Regional constraint	o/e 1.08	unconstrained · MANE · 7,328 bp · p 0.2 · regional, not allelic
Overall
CADD	0.257	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 0.331% European (non-Finnish) · 2,965/894,806 alleles

Filtering AF 0.321% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.317%

Overall 0.267% 3,230/1,209,612 alleles · rare exomes 3,037/1,097,762 · genomes 193/111,850 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.441%	227
European (non-Finnish)grpmax	0.331%	302
Remaining individualsnot grpmax-eligible	0.275%	363
Finnishnot grpmax-eligible	0.0901%	1,110
South Asian	0.067%	1,493
African / African-American	0.0489%	2,044
Middle Eastern	0.046%	2,176
Ashkenazi Jewishnot grpmax-eligible	0.0363%	2,753
Admixed American	0.0283%	3,528

Amish 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: CDX4
Protein: p.Pro67Gln
Coding: c.200C>A
MANE Select: NM_005193
dbSNP: rs145092385
Type: single nucleotide variant
Location: chrX:73447453 (GRCh38)
Structure: AlphaFold pLDDT 63.87

Full CDX4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDX4 p.Pro67Ala Uncertain significance ★ ⚠ same residue
CDX4 p.Ala106Ser Uncertain significance ★ ⚠ same type
CDX4 p.Ala207Thr Uncertain significance ★ ⚠ same type
CDX4 p.Ala226Gly Uncertain significance ★ ⚠ same type
CDX4 p.Arg161Gly Uncertain significance ★ ⚠ same type
CDX4 p.Arg177His Uncertain significance ★ ⚠ same type
CDX4 p.Arg215Lys Uncertain significance ★ ⚠ same type
CDX4 p.Arg215Thr 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/cdx4-p-pro67gln (accessed [today's date]).

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