Is CD22 p.Arg669His (c.2006G>A) pathogenic?

CD22 p.Arg669His (c.2006G>A) is classified Conflicting classifications of pathogenicity in CD22 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-08). AlphaMissense: likely benign (0.0555); Rare (popmax 0.195%, amr).

How common is CD22 p.Arg669His (c.2006G>A) in the general population?

CD22 p.Arg669His (c.2006G>A) is rare (popmax 0.195%, amr) (gnomAD).

What do computational predictors say about CD22 p.Arg669His (c.2006G>A)?

AlphaMissense predicts likely benign (score 0.0555) — an in-silico prediction, not a clinical call.

CD22 p.Arg669His

c.2006G>A · rs140037563 · VCV626074

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0555 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.195%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0555	likely benign
REVEL	0.009	strongly benign-leaning
SaProt	LLR -8.16	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 -1.1	GERP -4.7
Regional constraint	o/e 0.88	unconstrained · MANE · 15 kb · p 7.1e-05 · regional, not allelic
Overall
CADD	0.824	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 0.195% Admixed American · 117/59,958 alleles

Filtering AF 0.172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.17%

Overall 0.153% 2,467/1,613,524 alleles · rare exomes 2,281/1,461,522 · genomes 186/152,002 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.195%	512
Remaining individualsnot grpmax-eligible	0.181%	553
European (non-Finnish)	0.179%	560
Finnishnot grpmax-eligible	0.147%	679
Middle Eastern	0.066%	1,514
Ashkenazi Jewishnot grpmax-eligible	0.0271%	3,697
African / African-American	0.0267%	3,747
East Asian	0.00669%	14,957
South Asian	0.0011%	91,040

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: CD22
Protein: p.Arg669His
Coding: c.2006G>A
MANE Select: NM_001771
dbSNP: rs140037563
Type: single nucleotide variant
Location: chr19:35341936 (GRCh38)
Gene constraint: LOEUF 0.639 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.33 · 7 PDB
Residue 669: a β-strand; the ig-like c2-type 6 domain; a UniProt-annotated variant site (in)

Full CD22 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD22 p.Ala391Thr Benign ★★ same type
CD22 p.Cys265= Benign ★★ same type
CD22 p.Gly551Arg Benign ★★ same type
CD22 p.Gly727Ser Likely benign ★★ same type
CD22 p.Pro681= Benign ★★ same type
CD22 p.Ala17Val Uncertain significance ★ ⚠ same type
CD22 p.Ala498Ser Uncertain significance ★ ⚠ same type
CD22 p.Ala656Thr Uncertain significance ★ ⚠ 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/cd22-p-arg669his (accessed [today's date]).

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