Is CD22 p.Pro681= (c.2043G>A) pathogenic?

CD22 p.Pro681= (c.2043G>A) is classified Benign in CD22 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). Rare (popmax 0.949%, nfe).

How common is CD22 p.Pro681= (c.2043G>A) in the general population?

CD22 p.Pro681= (c.2043G>A) is rare (popmax 0.949%, nfe) (gnomAD).

CD22 p.Pro681=

c.2043G>A · rs7259477 · VCV719268

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.949%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -4.4	GERP -4.7
Overall
CADD	1.154	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.949% European (non-Finnish) · 11,176/1,177,790 alleles

Filtering AF 0.934% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.928%

Overall 0.793% 12,782/1,611,136 alleles · rare exomes 11,878/1,458,810 · genomes 904/152,326 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.29%	77
European (non-Finnish)grpmax	0.949%	105
Amishnot grpmax-eligible	0.877%	114
Remaining individualsnot grpmax-eligible	0.677%	148
Admixed American	0.484%	207
Finnishnot grpmax-eligible	0.307%	326
Middle Eastern	0.231%	432
African / African-American	0.177%	564
South Asian	0.172%	582
East Asian	0.0134%	7,469

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro681=
Coding: c.2043G>A
MANE Select: NM_001771
dbSNP: rs7259477
Type: single nucleotide variant
Location: chr19:35344836 (GRCh38)
Gene constraint: LOEUF 0.639 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.33 · 7 PDB

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.Ala17Val Uncertain significance ★ ⚠ same type
CD22 p.Ala498Ser Uncertain significance ★ ⚠ same type
CD22 p.Ala656Thr Uncertain significance ★ ⚠ same type
CD22 p.Ala702Thr 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-pro681 (accessed [today's date]).

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