Is CRELD1 p.Trp75Arg (c.223T>C) pathogenic?

CRELD1 p.Trp75Arg (c.223T>C) is classified Pathogenic in CRELD1 (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely pathogenic (0.9774); Absent from gnomAD v4.1; Associated with congenital heart defects, multiple types, 4.

What condition is associated with CRELD1 p.Trp75Arg (c.223T>C)?

CRELD1 p.Trp75Arg (c.223T>C) is associated with congenital heart defects, multiple types, 4 (ClinVar).

How common is CRELD1 p.Trp75Arg (c.223T>C) in the general population?

CRELD1 p.Trp75Arg (c.223T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CRELD1 p.Trp75Arg (c.223T>C)?

AlphaMissense predicts likely pathogenic (score 0.9774) — an in-silico prediction, not a clinical call.

CRELD1 p.Trp75Arg

c.223T>C · rs2470480014 · VCV2574123

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9774 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

congenital heart defects, multiple types, 4

Computational evidence

Protein change
AlphaMissense	0.9774	likely pathogenic ✓ concordant with ClinVar
REVEL	0.483	indeterminate
SaProt	LLR -13.88	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 10 kb · p 0.081 · regional, not allelic
Overall
CADD	29.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CRELD1
Protein: p.Trp75Arg
Coding: c.223T>C
MANE Select: NM_001077415
dbSNP: rs2470480014
Type: single nucleotide variant
Location: chr3:9934883 (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

congenital heart defects, multiple types, 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CRELD1 p.Arg288Leu Pathogenic ⚠ same condition
CRELD1 c.460+1G>A Likely pathogenic ★★ same type
CRELD1 c.1049-283C>T Uncertain significance ★★ same type
CRELD1 c.1049-376T>G Uncertain significance ★★ same type
CRELD1 c.1049-401C>T Uncertain significance ★★ same type
CRELD1 p.Arg107Cys Uncertain significance ★★ ⚠ same type
CRELD1 p.Arg175Gln Uncertain significance ★★ ⚠ same type
CRELD1 p.Asn72Ser 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/creld1-p-trp75arg (accessed [today's date]).

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