Is CD93 p.Met187Ile (c.561G>A) pathogenic?

CD93 p.Met187Ile (c.561G>A) is classified Uncertain significance in CD93 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-04-26). AlphaMissense: likely pathogenic (0.7679); Very rare (popmax 8.48e-05%, nfe); Associated with CD93-related disorder.

What condition is associated with CD93 p.Met187Ile (c.561G>A)?

CD93 p.Met187Ile (c.561G>A) is associated with CD93-related disorder (ClinVar).

How common is CD93 p.Met187Ile (c.561G>A) in the general population?

CD93 p.Met187Ile (c.561G>A) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CD93 p.Met187Ile (c.561G>A)?

AlphaMissense predicts likely pathogenic (score 0.7679) — an in-silico prediction, not a clinical call.

CD93 p.Met187Ile

c.561G>A · VCV3346567

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7679 · ACMG-weighted

gnomAD v4.1

Rare

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

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CD93-related disorder

Computational evidence

Protein change
AlphaMissense	0.7679	likely pathogenic
REVEL	0.247	benign-leaning
SaProt	LLR -6.32	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 2,239 bp · p 0.011 · regional, not allelic
Overall
CADD	26.3	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

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,778 alleles

Overall 6.85e-05% 1/1,460,558 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: CD93
Protein: p.Met187Ile
Coding: c.561G>A
MANE Select: NM_012072
Type: single nucleotide variant
Location: chr20:23085632 (GRCh38)
Gene constraint: LOEUF 1.237 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.07 · 2 PDB

Full CD93 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CD93-related disorder

Similar variants

CD93 p.Arg634Ter Uncertain significance ★ same condition
CD93 p.Arg496Cys Likely benign same condition
CD93 p.Arg496His Likely benign same condition
CD93 p.Ser41= Likely benign same condition
CD93 p.Val117Gly Benign ⚠ same condition
CD93 p.Glu484del Likely benign same condition
CD93 p.Arg496= Benign/Likely benign ★★ same type
CD93 p.Gly448= Benign ★★ 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/cd93-p-met187ile (accessed [today's date]).

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