Is CD93 p.Arg496= (c.1488T>C) pathogenic?

CD93 p.Arg496= (c.1488T>C) is classified Benign/Likely benign in CD93 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-28). Common (popmax 83%, amr) — too common for a highly-penetrant pathogenic allele.

CD93 p.Arg496=

Q: How common is CD93 p.Arg496= (c.1488T>C) in the general population?

CD93 p.Arg496= (c.1488T>C) is common (popmax 83%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1488T>C · rs3746732 · VCV2688438

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 83%, amr) — too common for a highly-penetrant pathogenic allele

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 -0.39	GERP -3.1
Overall
CADD	0.727	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 83% Admixed American · 47,063/56,716 alleles

Filtering AF 82.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 82.1%

Overall 75.3% 1,196,396/1,588,624 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	95.9%	1
Admixed Americangrpmax	83%	1
East Asian	82.3%	1
Middle Eastern	80.7%	1
Ashkenazi Jewishnot grpmax-eligible	79.9%	1
South Asian	77.6%	1
Remaining individualsnot grpmax-eligible	76.3%	1
African / African-American	76.1%	1
European (non-Finnish)	74.6%	1
Finnishnot grpmax-eligible	69.3%	1

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg496=
Coding: c.1488T>C
MANE Select: NM_012072
dbSNP: rs3746732
Type: single nucleotide variant
Location: chr20:23084705 (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

Similar variants

CD93 p.Arg496Cys Likely benign same residue
CD93 p.Arg496His Likely benign same residue
CD93 p.Gly448= Benign ★★ same type
CD93 p.His551= Likely benign ★★ same type
CD93 p.Pro541Ser Benign/Likely benign ★★ same type
CD93 p.Ser520Leu Benign ★★ same type
CD93 p.Thr493Ile Benign/Likely benign ★★ same type
CD93 p.Val428Leu 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-arg496 (accessed [today's date]).

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