Is CRELD1 p.Asn22= (c.66C>T) pathogenic?

CRELD1 p.Asn22= (c.66C>T) is classified Likely benign in CRELD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-25). Very rare (popmax 8.48e-05%, nfe); Associated with atrioventricular septal defect, susceptibility to, 2.

What condition is associated with CRELD1 p.Asn22= (c.66C>T)?

CRELD1 p.Asn22= (c.66C>T) is associated with atrioventricular septal defect, susceptibility to, 2 (ClinVar).

How common is CRELD1 p.Asn22= (c.66C>T) in the general population?

CRELD1 p.Asn22= (c.66C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

CRELD1 p.Asn22=

c.66C>T · rs1403824321 · VCV1606950

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

atrioventricular septal defect, susceptibility to, 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.41	GERP -2.2, phastCons 0.001
Overall
CADD	6.964	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,572 alleles

Overall 6.84e-05% 1/1,461,278 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: CRELD1
Protein: p.Asn22=
Coding: c.66C>T
MANE Select: NM_001077415
dbSNP: rs1403824321
Type: single nucleotide variant
Location: chr3:9934504 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.68

Full CRELD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

atrioventricular septal defect, susceptibility to, 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CRELD1 c.1049-283C>T Uncertain significance ★★ same condition
CRELD1 c.1049-376T>G Uncertain significance ★★ same condition
CRELD1 c.1049-401C>T Uncertain significance ★★ same condition
CRELD1 p.Arg107Cys Uncertain significance ★★ ⚠ same condition
CRELD1 p.Arg175Gln Uncertain significance ★★ ⚠ same condition
CRELD1 p.Asn72Ser Uncertain significance ★★ ⚠ same condition
CRELD1 p.Cys221Arg Uncertain significance ★★ ⚠ same condition
CRELD1 p.Cys292Arg Uncertain significance ★★ ⚠ same condition

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/creld1-p-asn22 (accessed [today's date]).

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