Is CXADR p.Arg90Gln (c.269G>A) pathogenic?

CXADR p.Arg90Gln (c.269G>A) is classified Uncertain significance in CXADR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-21). AlphaMissense: likely pathogenic (0.7245); Very rare (popmax 0.00833%, amr).

How common is CXADR p.Arg90Gln (c.269G>A) in the general population?

CXADR p.Arg90Gln (c.269G>A) is very rare (popmax 0.00833%, amr) (gnomAD).

What do computational predictors say about CXADR p.Arg90Gln (c.269G>A)?

AlphaMissense predicts likely pathogenic (score 0.7245) — an in-silico prediction, not a clinical call.

CXADR p.Arg90Gln

c.269G>A · VCV3837583

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7245 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7245	likely pathogenic
REVEL	0.758	pathogenic-leaning
SaProt	LLR -10.93	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 8.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 46 kb · p 0.0096 · regional, not allelic
Overall
CADD	28.9	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 0.00833% Admixed American · 5/59,990 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.000821% 12/1,461,516 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	11,998
Finnishnot grpmax-eligible	0.00469%	21,327
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,590
European (non-Finnish)	0.000254%	393,258

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.Arg90Gln
Coding: c.269G>A
MANE Select: NM_001338
Type: single nucleotide variant
Location: chr21:17551807 (GRCh38)
Gene constraint: LOEUF 0.751 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.51 · 23 PDB
Residue 90: a disulfide bond; a turn; the ig-like c2-type 1 domain

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.Asn298Ser 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-arg90gln (accessed [today's date]).

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