Is CD22 p.Ser562Cys (c.1685C>G) pathogenic?

CD22 p.Ser562Cys (c.1685C>G) is classified Uncertain significance in CD22 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-07). AlphaMissense: likely benign (0.2413); Very rare (popmax 0.00666%, amr).

How common is CD22 p.Ser562Cys (c.1685C>G) in the general population?

CD22 p.Ser562Cys (c.1685C>G) is very rare (popmax 0.00666%, amr) (gnomAD).

What do computational predictors say about CD22 p.Ser562Cys (c.1685C>G)?

AlphaMissense predicts likely benign (score 0.2413) — an in-silico prediction, not a clinical call.

CD22 p.Ser562Cys

c.1685C>G · rs750286044 · VCV2306234

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2413 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00666%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2413	likely benign
REVEL	0.115	moderately benign-leaning
SaProt	LLR -10.33	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	Δ0.57	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 4.8	GERP 1.4, phastCons 0.87
Regional constraint	o/e 0.88	unconstrained · MANE · 15 kb · p 7.1e-05 · regional, not allelic
Overall
CADD	24.0	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 0.00666% Admixed American · 4/60,026 alleles

Filtering AF 0.00225% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000248% 4/1,614,088 alleles · very rare exomes 4/1,461,784 · genomes 0/152,304 · joint denominator

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.Ser562Cys
Coding: c.1685C>G
MANE Select: NM_001771
dbSNP: rs750286044
Type: single nucleotide variant
Location: chr19:35341520 (GRCh38)
Gene constraint: LOEUF 0.639 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.33 · 7 PDB
Residue 562: the ig-like c2-type 5 domain

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-ser562cys (accessed [today's date]).

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