Is CD93 p.Val494Met (c.1480G>A) pathogenic?

CD93 p.Val494Met (c.1480G>A) is classified Uncertain significance in CD93 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-13). AlphaMissense: likely benign (0.0946); Ultra-rare (popmax 0.017%, sas).

How common is CD93 p.Val494Met (c.1480G>A) in the general population?

CD93 p.Val494Met (c.1480G>A) is ultra-rare (popmax 0.017%, sas) (gnomAD).

What do computational predictors say about CD93 p.Val494Met (c.1480G>A)?

AlphaMissense predicts likely benign (score 0.0946) — an in-silico prediction, not a clinical call.

CD93 p.Val494Met

c.1480G>A · VCV3998370

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0946 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.017%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0946	likely benign
REVEL	0.271	benign-leaning
SaProt	LLR -8.22	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 -7	GERP -3.5
Regional constraint	o/e 1.09	unconstrained · MANE · 2,239 bp · p 0.011 · regional, not allelic
Overall
CADD	0.011	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 0.017% South Asian · 15/88,230 alleles

Filtering AF 0.0105% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00846%

Overall 0.00263% 42/1,594,628 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.017%	5,882
Admixed American	0.00523%	19,109
African / African-American	0.0027%	37,057
European (non-Finnish)	0.00188%	53,240

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.Val494Met
Coding: c.1480G>A
MANE Select: NM_012072
Type: single nucleotide variant
Location: chr20:23084713 (GRCh38)
Gene constraint: LOEUF 1.237 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.07 · 2 PDB
Residue 494: 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-val494met (accessed [today's date]).

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