Is CD93 p.Val543Ile (c.1627G>A) pathogenic?

CD93 p.Val543Ile (c.1627G>A) is classified Likely benign in CD93 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-11-20). AlphaMissense: likely benign (0.064); Rare (popmax 0.297%, afr).

How common is CD93 p.Val543Ile (c.1627G>A) in the general population?

CD93 p.Val543Ile (c.1627G>A) is rare (popmax 0.297%, afr) (gnomAD).

What do computational predictors say about CD93 p.Val543Ile (c.1627G>A)?

AlphaMissense predicts likely benign (score 0.064) — an in-silico prediction, not a clinical call.

CD93 p.Val543Ile

c.1627G>A · rs150881468 · VCV3051666

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.064 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.297%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.064	likely benign
REVEL	0.206	benign-leaning
SaProt	LLR -7.19	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 -5.5	GERP -3.1
Regional constraint	o/e 1.09	unconstrained · MANE · 2,239 bp · p 0.011 · regional, not allelic
Overall
CADD	0.007	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 0.297% African / African-American · 223/74,998 alleles

Filtering AF 0.265% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.253%

Overall 0.021% 339/1,612,406 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.297%	336
Admixed American	0.0801%	1,249
Remaining individualsnot grpmax-eligible	0.016%	6,246
South Asian	0.0066%	15,154
East Asian	0.00446%	22,424
European (non-Finnish)	0.00416%	24,061
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,560

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.Val543Ile
Coding: c.1627G>A
MANE Select: NM_012072
dbSNP: rs150881468
Type: single nucleotide variant
Location: chr20:23084566 (GRCh38)
Gene constraint: LOEUF 1.237 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.07 · 2 PDB
Residue 543: 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-val543ile (accessed [today's date]).

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