Is CRELD1 p.Ala352Val (c.1055C>T) pathogenic?

CRELD1 p.Ala352Val (c.1055C>T) is classified Uncertain significance in CRELD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-27). AlphaMissense: likely benign (0.1056); Very rare (popmax 8.48e-05%, nfe).

How common is CRELD1 p.Ala352Val (c.1055C>T) in the general population?

CRELD1 p.Ala352Val (c.1055C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CRELD1 p.Ala352Val (c.1055C>T)?

AlphaMissense predicts likely benign (score 0.1056) — an in-silico prediction, not a clinical call.

CRELD1 p.Ala352Val

c.1055C>T · rs1575654644 · VCV2579857

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1056 · ACMG-weighted

gnomAD v4.1

Rare

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

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1056	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	LLR -6.26	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 0.14, phastCons 0.99
Regional constraint	o/e 0.92	unconstrained · MANE · 10 kb · p 0.081 · regional, not allelic
Overall
CADD	15.71	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,906 alleles

Overall 6.84e-05% 1/1,461,576 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.Ala352Val
Coding: c.1055C>T
MANE Select: NM_001077415
dbSNP: rs1575654644
Type: single nucleotide variant
Location: chr3:9944371 (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

Similar variants

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
CRELD1 p.Cys221Arg 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-ala352val (accessed [today's date]).

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