Is CD93 p.Pro171Ala (c.511C>G) pathogenic?

CD93 p.Pro171Ala (c.511C>G) is classified Uncertain significance in CD93 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-31). AlphaMissense: likely benign (0.0896); Ultra-rare (popmax 0.0121%, sas).

How common is CD93 p.Pro171Ala (c.511C>G) in the general population?

CD93 p.Pro171Ala (c.511C>G) is ultra-rare (popmax 0.0121%, sas) (gnomAD).

What do computational predictors say about CD93 p.Pro171Ala (c.511C>G)?

AlphaMissense predicts likely benign (score 0.0896) — an in-silico prediction, not a clinical call.

CD93 p.Pro171Ala

c.511C>G · VCV4223086

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0896 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0121%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0896	likely benign
REVEL	0.358	indeterminate
SaProt	LLR -7.01	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 0.87, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 2,239 bp · p 0.011 · regional, not allelic
Overall
CADD	14.41	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 0.0121% South Asian · 11/90,992 alleles

Filtering AF 0.00677% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00522%

Overall 0.000931% 15/1,610,604 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0121%	8,272
African / African-American	0.00134%	74,796
European (non-Finnish)	0.000254%	393,093

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.Pro171Ala
Coding: c.511C>G
MANE Select: NM_012072
Type: single nucleotide variant
Location: chr20:23085682 (GRCh38)
Gene constraint: LOEUF 1.237 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.07 · 2 PDB
Residue 171: the c-type lectin domain

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-pro171ala (accessed [today's date]).

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