Is CD33 p.Asn113Asp (c.337A>G) pathogenic?

CD33 p.Asn113Asp (c.337A>G) is classified Uncertain significance in CD33 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-17). AlphaMissense: likely benign (0.0894); Ultra-rare (popmax 0.0684%, sas).

How common is CD33 p.Asn113Asp (c.337A>G) in the general population?

CD33 p.Asn113Asp (c.337A>G) is ultra-rare (popmax 0.0684%, sas) (gnomAD).

What do computational predictors say about CD33 p.Asn113Asp (c.337A>G)?

AlphaMissense predicts likely benign (score 0.0894) — an in-silico prediction, not a clinical call.

CD33 p.Asn113Asp

c.337A>G · rs761220053 · VCV3140550

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0894 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0684%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0894	likely benign
REVEL	0.05	moderately benign-leaning
SaProt	LLR -9.18	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 -1.8
Regional constraint	o/e 0.91	unconstrained · MANE · 15 kb · p 0.052 · regional, not allelic
Overall
CADD	0.174	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 0.0684% South Asian · 62/90,594 alleles

Filtering AF 0.0547% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0498%

Overall 0.00404% 65/1,610,276 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0684%	1,461
Remaining individualsnot grpmax-eligible	0.0016%	62,324
European (non-Finnish)	0.00017%	589,074

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.Asn113Asp
Coding: c.337A>G
MANE Select: NM_001772
dbSNP: rs761220053
Type: single nucleotide variant
Location: chr19:51225517 (GRCh38)
Gene constraint: LOEUF 1.072 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.30 · 11 PDB
Residue 113: a disulfide bond; the ig-like v-type domain

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-asn113asp (accessed [today's date]).

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