Is CDX1 p.Pro104Ser (c.310C>T) pathogenic?

CDX1 p.Pro104Ser (c.310C>T) is classified Uncertain significance in CDX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-07). AlphaMissense: likely benign (0.069); Rare (popmax 0.157%, sas).

How common is CDX1 p.Pro104Ser (c.310C>T) in the general population?

CDX1 p.Pro104Ser (c.310C>T) is rare (popmax 0.157%, sas) (gnomAD).

What do computational predictors say about CDX1 p.Pro104Ser (c.310C>T)?

AlphaMissense predicts likely benign (score 0.069) — an in-silico prediction, not a clinical call.

CDX1 p.Pro104Ser

c.310C>T · rs552110612 · VCV3141759

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.069 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.157%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.069	likely benign
REVEL	0.105	moderately benign-leaning
SaProt	LLR -7.09	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 7.5	GERP 1.5, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 17 kb · p 0.73 · regional, not allelic
Overall
CADD	24.3	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 0.157% South Asian · 53/33,686 alleles

Filtering AF 0.123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.111%

Overall 0.00465% 59/1,270,000 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.157%	636
Remaining individualsnot grpmax-eligible	0.00846%	11,826
East Asian	0.00321%	31,186
European (non-Finnish)	9.87e-05%	1,013,166

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.Pro104Ser
Coding: c.310C>T
MANE Select: NM_001804
dbSNP: rs552110612
Type: single nucleotide variant
Location: chr5:150167186 (GRCh38)
Gene constraint: LOEUF 1.625 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.02 · 2 PDB
Residue 104: the 'disordered' region

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

Similar variants

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
CDX1 p.Arg152Trp 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-pro104ser (accessed [today's date]).

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