Is CD33 p.Ser128Asn (c.383G>A) pathogenic?

CD33 p.Ser128Asn (c.383G>A) is classified Benign in CD33 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-05-15). AlphaMissense: likely benign (0.2182); Low-frequency (popmax 3.15%, afr).

How common is CD33 p.Ser128Asn (c.383G>A) in the general population?

CD33 p.Ser128Asn (c.383G>A) is low-frequency (popmax 3.15%, afr) (gnomAD).

What do computational predictors say about CD33 p.Ser128Asn (c.383G>A)?

AlphaMissense predicts likely benign (score 0.2182) — an in-silico prediction, not a clinical call.

CD33 p.Ser128Asn

c.383G>A · rs34919259 · VCV775424

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2182 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.15%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2182	likely benign
REVEL	0.027	moderately benign-leaning
SaProt	LLR -6.84	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 -20	GERP -3.4
Regional constraint	o/e 0.91	unconstrained · MANE · 15 kb · p 0.052 · regional, not allelic
Overall
CADD	0.001	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 3.15% African / African-American · 2,326/73,940 alleles

Filtering AF 3.04% ClinGen BA1/BS1 input FAF95, joint · FAF99 3%

Overall 0.17% 2,673/1,574,646 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.15%	32
Admixed American	0.229%	438
Middle Eastern	0.205%	487
Remaining individualsnot grpmax-eligible	0.199%	502
South Asian	0.00836%	11,959
European (non-Finnish)	0.00681%	14,690

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.Ser128Asn
Coding: c.383G>A
MANE Select: NM_001772
dbSNP: rs34919259
Type: single nucleotide variant
Location: chr19:51225563 (GRCh38)
Gene constraint: LOEUF 1.072 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.30 · 11 PDB
Residue 128: a disulfide bond; a UniProt-annotated variant site (in); the ig-like v-type domain; a β-strand

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

Similar variants

CD33 p.Asp51Asn Uncertain significance ★★ ⚠ same type
CD33 c.924+295A>G Benign ★★ same type
CD33 c.924+296C>T Benign ★★ same type
CD33 c.924+2T>C Benign ★★ same type
CD33 c.924+469G>C Benign ★★ same type
CD33 c.*201G>C Benign ★★ same type
CD33 p.Ala14Val Benign ★★ ⚠ same type
CD33 p.Ala65Pro 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-ser128asn (accessed [today's date]).

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