Is CD93 p.Arg496His (c.1487G>A) pathogenic?

CD93 p.Arg496His (c.1487G>A) is classified Likely benign in CD93 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-04-12). AlphaMissense: likely benign (0.0776); Rare (popmax 0.463%, eas); Associated with CD93-related disorder.

What condition is associated with CD93 p.Arg496His (c.1487G>A)?

CD93 p.Arg496His (c.1487G>A) is associated with CD93-related disorder (ClinVar).

How common is CD93 p.Arg496His (c.1487G>A) in the general population?

CD93 p.Arg496His (c.1487G>A) is rare (popmax 0.463%, eas) (gnomAD).

What do computational predictors say about CD93 p.Arg496His (c.1487G>A)?

AlphaMissense predicts likely benign (score 0.0776) — an in-silico prediction, not a clinical call.

CD93 p.Arg496His

c.1487G>A · rs570911199 · VCV3060757

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0776 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.463%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CD93-related disorder

Computational evidence

Protein change
AlphaMissense	0.0776	likely benign
REVEL	0.105	moderately benign-leaning
SaProt	LLR -7.30	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 1.4	GERP -3.2, phastCons 0.005
Regional constraint	o/e 1.09	unconstrained · MANE · 2,239 bp · p 0.011 · regional, not allelic
Overall
CADD	11.36	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 0.463% East Asian · 207/44,666 alleles

Filtering AF 0.412% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.392%

Overall 0.0218% 347/1,589,980 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.463%	216
African / African-American	0.027%	3,702
South Asian	0.0114%	8,748
European (non-Finnish)	0.00856%	11,688
Admixed American	0.00704%	14,195
Remaining individualsnot grpmax-eligible	0.00652%	15,331
Finnishnot grpmax-eligible	0.0032%	31,239

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.Arg496His
Coding: c.1487G>A
MANE Select: NM_012072
dbSNP: rs570911199
Type: single nucleotide variant
Location: chr20:23084706 (GRCh38)
Gene constraint: LOEUF 1.237 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.07 · 2 PDB
Residue 496: the 'disordered' region

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

Disease context

CD93-related disorder

Similar variants

CD93 p.Arg496Cys Likely benign same residue
CD93 p.Arg496= Benign/Likely benign ★★ same residue
CD93 p.Arg634Ter Uncertain significance ★ same condition
CD93 p.Met187Ile Uncertain significance ⚠ same condition
CD93 p.Ser41= Likely benign same condition
CD93 p.Val117Gly Benign ⚠ same condition
CD93 p.Glu484del Likely benign same condition
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-arg496his (accessed [today's date]).

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