Is CD33 p.Arg119Trp (c.355C>T) pathogenic?

CD33 p.Arg119Trp (c.355C>T) is classified Uncertain significance in CD33 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-01). AlphaMissense: likely benign (0.1571); Ultra-rare (popmax 0.0196%, nfe).

How common is CD33 p.Arg119Trp (c.355C>T) in the general population?

CD33 p.Arg119Trp (c.355C>T) is ultra-rare (popmax 0.0196%, nfe) (gnomAD).

What do computational predictors say about CD33 p.Arg119Trp (c.355C>T)?

AlphaMissense predicts likely benign (score 0.1571) — an in-silico prediction, not a clinical call.

CD33 p.Arg119Trp

c.355C>T · rs202143203 · VCV2349729

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1571 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0196%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1571	likely benign
REVEL	0.363	indeterminate
SaProt	LLR -10.38	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -3.7
Regional constraint	o/e 0.91	unconstrained · MANE · 15 kb · p 0.052 · regional, not allelic
Overall
CADD	12.04	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 0.0196% European (non-Finnish) · 230/1,172,544 alleles

Filtering AF 0.0175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0167%

Overall 0.0152% 243/1,599,290 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0196%	5,098
Remaining individualsnot grpmax-eligible	0.0129%	7,727
African / African-American	0.00537%	18,614
South Asian	0.00113%	88,698

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.Arg119Trp
Coding: c.355C>T
MANE Select: NM_001772
dbSNP: rs202143203
Type: single nucleotide variant
Location: chr19:51225535 (GRCh38)
Gene constraint: LOEUF 1.072 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.30 · 11 PDB
Residue 119: a binding site; a disulfide bond; 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-arg119trp (accessed [today's date]).

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