Is CD33 p.Val267Ile (c.799G>A) pathogenic?

CD33 p.Val267Ile (c.799G>A) is classified Benign in CD33 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-06-10). AlphaMissense: likely benign (0.0854); Common (popmax 11.9%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about CD33 p.Val267Ile (c.799G>A)?

AlphaMissense predicts likely benign (score 0.0854) — an in-silico prediction, not a clinical call.

CD33 p.Val267Ile

Q: How common is CD33 p.Val267Ile (c.799G>A) in the general population?

CD33 p.Val267Ile (c.799G>A) is common (popmax 11.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.799G>A · rs58981829 · VCV1239578

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0854 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 11.9%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0854	likely benign
REVEL	0.017	moderately benign-leaning
SaProt	LLR -6.62	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 -1.9	GERP -0.27
Regional constraint	o/e 0.91	unconstrained · MANE · 15 kb · p 0.052 · regional, not allelic
Overall
CADD	0.621	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 11.9% African / African-American · 8,956/75,008 alleles

Filtering AF 11.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 11.6%

Overall 0.642% 10,370/1,614,170 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	11.9%	8
Middle Eastern	1.3%	77
Admixed American	0.861%	116
Remaining individualsnot grpmax-eligible	0.811%	123
South Asian	0.0253%	3,960
European (non-Finnish)	0.0244%	4,097

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.Val267Ile
Coding: c.799G>A
MANE Select: NM_001772
dbSNP: rs58981829
Type: single nucleotide variant
Location: chr19:51235210 (GRCh38)
Gene constraint: LOEUF 1.072 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.30 · 11 PDB
Residue 267: a UniProt-annotated variant site (in); an α-helix

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

Similar variants

CD33 p.Val267Ala Uncertain significance ★ ⚠ same residue
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

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-val267ile (accessed [today's date]).

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