Is CRELD2 p.Ser194Arg (c.582C>A) pathogenic?

CRELD2 p.Ser194Arg (c.582C>A) is classified Uncertain significance in CRELD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-20). AlphaMissense: likely pathogenic (0.6405); Absent from gnomAD v4.1.

How common is CRELD2 p.Ser194Arg (c.582C>A) in the general population?

CRELD2 p.Ser194Arg (c.582C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CRELD2 p.Ser194Arg (c.582C>A)?

AlphaMissense predicts likely pathogenic (score 0.6405) — an in-silico prediction, not a clinical call.

CRELD2 p.Ser194Arg

c.582C>A · rs2519312468 · VCV3077396

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6405 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6405	likely pathogenic
REVEL	0.502	indeterminate
SaProt	LLR -10.77	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 -0.36	GERP -1.1
Regional constraint	o/e 0.99	unconstrained · MANE · 8,534 bp · p 0.81 · regional, not allelic
Overall
CADD	20.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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: CRELD2
Protein: p.Ser194Arg
Coding: c.582C>A
MANE Select: NM_024324
dbSNP: rs2519312468
Type: single nucleotide variant
Location: chr22:49921751 (GRCh38)
Gene constraint: LOEUF 1.119 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.63

Full CRELD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CRELD2 p.Ala236= Benign ★★ same type
CRELD2 p.Cys294= Benign/Likely benign ★★ same type
CRELD2 p.Gly162= Benign ★★ same type
CRELD2 c.593-181G>T Uncertain significance ★ same type
CRELD2 c.593-202A>T Uncertain significance ★ same type
CRELD2 c.593-208G>T Uncertain significance ★ same type
CRELD2 c.593-222C>T Uncertain significance ★ same type
CRELD2 c.593-228G>A 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/creld2-p-ser194arg (accessed [today's date]).

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