Is CRELD1 p.Phe200= (c.600T>C) pathogenic?

CRELD1 p.Phe200= (c.600T>C) is classified Likely benign in CRELD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-25). Very rare (popmax 0.00746%, nfe); Associated with atrioventricular septal defect, susceptibility to, 2.

What condition is associated with CRELD1 p.Phe200= (c.600T>C)?

CRELD1 p.Phe200= (c.600T>C) is associated with atrioventricular septal defect, susceptibility to, 2 (ClinVar).

How common is CRELD1 p.Phe200= (c.600T>C) in the general population?

CRELD1 p.Phe200= (c.600T>C) is very rare (popmax 0.00746%, nfe) (gnomAD).

CRELD1 p.Phe200=

c.600T>C · rs143534215 · VCV1662012

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00746%, 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 1.1	GERP -3.4, phastCons 1
Overall
CADD	14.79	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00746% European (non-Finnish) · 88/1,180,002 alleles

Filtering AF 0.00615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00573%

Overall 0.00558% 90/1,613,964 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00746%	13,409
Admixed American	0.00167%	59,996
Remaining individualsnot grpmax-eligible	0.0016%	62,490

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.Phe200=
Coding: c.600T>C
MANE Select: NM_001077415
dbSNP: rs143534215
Type: single nucleotide variant
Location: chr3:9940989 (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-phe200 (accessed [today's date]).

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