Is CDX4 p.Pro105Thr (c.313C>A) pathogenic?

CDX4 p.Pro105Thr (c.313C>A) is classified Uncertain significance in CDX4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-13). AlphaMissense: likely benign (0.0676); Rare (popmax 0.105%, afr).

How common is CDX4 p.Pro105Thr (c.313C>A) in the general population?

CDX4 p.Pro105Thr (c.313C>A) is rare (popmax 0.105%, afr) (gnomAD).

What do computational predictors say about CDX4 p.Pro105Thr (c.313C>A)?

AlphaMissense predicts likely benign (score 0.0676) — an in-silico prediction, not a clinical call.

CDX4 p.Pro105Thr

c.313C>A · rs140116090 · VCV2412313

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0676 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.105%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0676	likely benign
REVEL	0.094	moderately benign-leaning
SaProt	LLR -6.30	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP 0.18, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 7,328 bp · p 0.2 · regional, not allelic
Overall
CADD	10.68	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.105% African / African-American · 60/57,249 alleles

Filtering AF 0.0835% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0758%

Overall 0.00636% 77/1,209,776 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.105%	954
Middle Eastern	0.0919%	1,089
Remaining individualsnot grpmax-eligible	0.0189%	5,288
Admixed American	0.00436%	22,929
European (non-Finnish)	0.000223%	447,513

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.Pro105Thr
Coding: c.313C>A
MANE Select: NM_005193
dbSNP: rs140116090
Type: single nucleotide variant
Location: chrX:73447566 (GRCh38)
Structure: AlphaFold pLDDT 63.87

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

Similar variants

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
CDX4 p.Arg270Cys 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-pro105thr (accessed [today's date]).

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