Is CXADR p.Thr288= (c.864G>C) pathogenic?

CXADR p.Thr288= (c.864G>C) is classified Likely benign in CXADR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-02). Very rare (popmax 0.000848%, nfe).

How common is CXADR p.Thr288= (c.864G>C) in the general population?

CXADR p.Thr288= (c.864G>C) is very rare (popmax 0.000848%, nfe) (gnomAD).

CXADR p.Thr288=

c.864G>C · VCV3837581

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000848%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.185	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.5	GERP -3.4
Overall
CADD	0.298	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000848% European (non-Finnish) · 10/1,179,850 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000684% 10/1,461,656 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.Thr288=
Coding: c.864G>C
MANE Select: NM_001338
Type: single nucleotide variant
Location: chr21:17565458 (GRCh38)
Gene constraint: LOEUF 0.751 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.51 · 23 PDB
Residue 288: the 'disordered' region

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-thr288 (accessed [today's date]).

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