Is CXADR p.Ser363Phe (c.1088C>T) pathogenic?

CXADR p.Ser363Phe (c.1088C>T) is classified Uncertain significance in CXADR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-18). AlphaMissense: likely pathogenic (0.7228); Very rare (popmax 0.00144%, nfe).

How common is CXADR p.Ser363Phe (c.1088C>T) in the general population?

CXADR p.Ser363Phe (c.1088C>T) is very rare (popmax 0.00144%, nfe) (gnomAD).

What do computational predictors say about CXADR p.Ser363Phe (c.1088C>T)?

AlphaMissense predicts likely pathogenic (score 0.7228) — an in-silico prediction, not a clinical call.

CXADR p.Ser363Phe

c.1088C>T · rs753870489 · VCV2331783

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7228 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00144%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7228	likely pathogenic
REVEL	0.606	indeterminate
SaProt	LLR -9.11	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.7, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 4,909 bp · p 0.0015 · regional, not allelic
Overall
CADD	25.3	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 0.00144% European (non-Finnish) · 17/1,179,796 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000718%

Overall 0.00105% 17/1,611,758 alleles · very rare

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: CXADR
Protein: p.Ser363Phe
Coding: c.1088C>T
MANE Select: NM_001338
dbSNP: rs753870489
Type: single nucleotide variant
Location: chr21:17565682 (GRCh38)
Gene constraint: LOEUF 0.751 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.51 · 23 PDB
Residue 363: a modified residue (phosphoserine)

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

Similar variants

CXADR p.Thr193= Benign ★★ same type
CXADR p.Ala144Val Uncertain significance ★ ⚠ same type
CXADR p.Arg217Lys Uncertain significance ★ ⚠ same type
CXADR p.Arg226Pro Uncertain significance ★ ⚠ same type
CXADR p.Arg264Cys Uncertain significance ★ ⚠ same type
CXADR p.Arg287Cys Uncertain significance ★ ⚠ same type
CXADR p.Arg328His Uncertain significance ★ ⚠ same type
CXADR p.Arg90Gln 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/cxadr-p-ser363phe (accessed [today's date]).

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