Is CD93 p.Thr493Ile (c.1478C>T) pathogenic?

CD93 p.Thr493Ile (c.1478C>T) is classified Benign/Likely benign in CD93 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-22). AlphaMissense: likely benign (0.0971); Low-frequency (popmax 1.53%, afr).

How common is CD93 p.Thr493Ile (c.1478C>T) in the general population?

CD93 p.Thr493Ile (c.1478C>T) is low-frequency (popmax 1.53%, afr) (gnomAD).

What do computational predictors say about CD93 p.Thr493Ile (c.1478C>T)?

AlphaMissense predicts likely benign (score 0.0971) — an in-silico prediction, not a clinical call.

CD93 p.Thr493Ile

c.1478C>T · rs79736225 · VCV734870

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0971 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.53%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0971	likely benign
REVEL	0.106	moderately benign-leaning
SaProt	LLR -8.77	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 0.096	GERP -2.1
Regional constraint	o/e 1.09	unconstrained · MANE · 2,239 bp · p 0.011 · regional, not allelic
Overall
CADD	1.065	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 1.53% African / African-American · 1,137/74,320 alleles

Filtering AF 1.46% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.43%

Overall 0.107% 1,707/1,596,720 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.53%	65
Middle Eastern	0.287%	349
Admixed American	0.18%	554
Remaining individualsnot grpmax-eligible	0.166%	604
European (non-Finnish)	0.0288%	3,468
South Asian	0.0079%	12,655
Ashkenazi Jewishnot grpmax-eligible	0.00713%	14,029

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.Thr493Ile
Coding: c.1478C>T
MANE Select: NM_012072
dbSNP: rs79736225
Type: single nucleotide variant
Location: chr20:23084715 (GRCh38)
Gene constraint: LOEUF 1.237 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.07 · 2 PDB
Residue 493: the 'disordered' region

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

Similar variants

CD93 p.Arg496= Benign/Likely benign ★★ same type
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.Val428Leu Benign ★★ same type
CD93 p.Ala214Val Uncertain significance ★ ⚠ same type
CD93 p.Ala24Pro 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/cd93-p-thr493ile (accessed [today's date]).

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