Is CRELD1 p.Pro31= (c.93C>T) pathogenic?

CRELD1 p.Pro31= (c.93C>T) is classified Benign/Likely benign in CRELD1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-09-15). Rare (popmax 0.506%, sas); Associated with atrioventricular septal defect, susceptibility to, 2.

What condition is associated with CRELD1 p.Pro31= (c.93C>T)?

CRELD1 p.Pro31= (c.93C>T) is associated with atrioventricular septal defect, susceptibility to, 2 (ClinVar).

How common is CRELD1 p.Pro31= (c.93C>T) in the general population?

CRELD1 p.Pro31= (c.93C>T) is rare (popmax 0.506%, sas) (gnomAD).

CRELD1 p.Pro31=

c.93C>T · rs199599039 · VCV1615675

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.506%, sas)

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 -0.14	GERP 0.12, phastCons 0.097
Overall
CADD	10.25	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.506% South Asian · 461/91,082 alleles

Filtering AF 0.468% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.453%

Overall 0.0476% 768/1,614,090 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.506%	198
Middle Eastern	0.346%	289
Remaining individualsnot grpmax-eligible	0.08%	1,250
European (non-Finnish)	0.0192%	5,221
Admixed American	0.0117%	8,574
African / African-American	0.00267%	37,519
Finnishnot grpmax-eligible	0.00156%	63,992

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.Pro31=
Coding: c.93C>T
MANE Select: NM_001077415
dbSNP: rs199599039
Type: single nucleotide variant
Location: chr3:9934531 (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-pro31 (accessed [today's date]).

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