Is CD93 p.Leu532Phe (c.1594C>T) pathogenic?

CD93 p.Leu532Phe (c.1594C>T) is classified Uncertain significance in CD93 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-11). AlphaMissense: likely benign (0.0922); Ultra-rare (popmax 0.0164%, mid).

How common is CD93 p.Leu532Phe (c.1594C>T) in the general population?

CD93 p.Leu532Phe (c.1594C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about CD93 p.Leu532Phe (c.1594C>T)?

AlphaMissense predicts likely benign (score 0.0922) — an in-silico prediction, not a clinical call.

CD93 p.Leu532Phe

c.1594C>T · VCV4650747

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0922 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0922	likely benign
REVEL	0.097	moderately benign-leaning
SaProt	LLR -7.99	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 0.45	GERP 1.4
Regional constraint	o/e 1.09	unconstrained · MANE · 2,239 bp · p 0.011 · regional, not allelic
Overall
CADD	3.826	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.00231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00202%

Overall 0.00248% 40/1,612,832 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
European (non-Finnish)	0.00314%	31,878
African / African-American	0.00267%	37,415

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.Leu532Phe
Coding: c.1594C>T
MANE Select: NM_012072
Type: single nucleotide variant
Location: chr20:23084599 (GRCh38)
Gene constraint: LOEUF 1.237 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.07 · 2 PDB
Residue 532: 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.Thr493Ile Benign/Likely benign ★★ same type
CD93 p.Val428Leu Benign ★★ same type
CD93 p.Ala214Val 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-leu532phe (accessed [today's date]).

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