Is CD93 p.Arg634Ter (c.1900C>T) pathogenic?

CD93 p.Arg634Ter (c.1900C>T) is classified Uncertain significance in CD93 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-05). Ultra-rare (popmax 0.0198%, sas); Associated with CD93-related disorder.

What condition is associated with CD93 p.Arg634Ter (c.1900C>T)?

CD93 p.Arg634Ter (c.1900C>T) is associated with CD93-related disorder (ClinVar).

How common is CD93 p.Arg634Ter (c.1900C>T) in the general population?

CD93 p.Arg634Ter (c.1900C>T) is ultra-rare (popmax 0.0198%, sas) (gnomAD).

CD93 p.Arg634Ter

c.1900C>T · rs753827669 · VCV2634918

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0198%, sas)

Conditions

CD93-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (1 of 2, 34 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
REVEL	0.042	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.1	GERP -1.7
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0198% South Asian · 18/91,090 alleles

Filtering AF 0.0127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0105%

Overall 0.00923% 149/1,613,888 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0198%	5,061
Admixed American	0.0183%	5,455
European (non-Finnish)	0.00949%	10,536
Remaining individualsnot grpmax-eligible	0.0064%	15,622
African / African-American	0.00401%	24,965
Finnishnot grpmax-eligible	0.00156%	63,904

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.Arg634Ter
Coding: c.1900C>T
MANE Select: NM_012072
dbSNP: rs753827669
Type: single nucleotide variant
Location: chr20:23084293 (GRCh38)
Gene constraint: LOEUF 1.237 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.07 · 2 PDB
Residue 634: 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.Arg634Gln Uncertain significance ★ ⚠ same residue
CD93 p.Arg634Leu Uncertain significance ★ ⚠ same residue
CD93 p.Met187Ile 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

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-arg634ter (accessed [today's date]).

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