Is CD33 p.Pro238fs (c.713_731del) pathogenic?

CD33 p.Pro238fs (c.713731del) is classified Likely benign in CD33 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2024-09-19). Low-frequency (popmax 2.29%, eas); Associated with CD33-related disorder.

What condition is associated with CD33 p.Pro238fs (c.713_731del)?

CD33 p.Pro238fs (c.713_731del) is associated with CD33-related disorder (ClinVar).

How common is CD33 p.Pro238fs (c.713_731del) in the general population?

CD33 p.Pro238fs (c.713_731del) is low-frequency (popmax 2.29%, eas) (gnomAD).

CD33 p.Pro238fs

c.713_731del · rs201473304 · VCV3056025

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

low-frequency (popmax 2.29%, eas)

Conditions

CD33-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.2	GERP -3.3
Overall
CADD	21.6	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.29% East Asian · 1,023/44,658 alleles

Filtering AF 2.17% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.13%

Overall 0.0682% 1,100/1,613,710 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	2.29%	44
Remaining individualsnot grpmax-eligible	0.0688%	1,453
South Asian	0.0176%	5,691
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,802
Admixed American	0.00333%	30,007
Finnishnot grpmax-eligible	0.00156%	64,004
African / African-American	0.00133%	75,028
European (non-Finnish)	0.00102%	98,324

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: CD33
Protein: p.Pro238fs
Coding: c.713_731del
MANE Select: NM_001772
dbSNP: rs201473304
Type: Deletion
Location: chr19:51226322 (GRCh38)
Gene constraint: LOEUF 1.072 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.30 · 11 PDB

Full CD33 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CD33-related disorder

Similar variants

CD33 p.Ile47_Pro48insAsnIle Uncertain significance same condition
CD33 p.Gly156fs Benign ★ 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/cd33-p-pro238fs (accessed [today's date]).

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