Is CD22 p.Ser618Ile (c.1853G>T) pathogenic?

CD22 p.Ser618Ile (c.1853G>T) is classified Uncertain significance in CD22 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-16). AlphaMissense: ambiguous (0.4561); Absent from gnomAD v4.1.

How common is CD22 p.Ser618Ile (c.1853G>T) in the general population?

CD22 p.Ser618Ile (c.1853G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD22 p.Ser618Ile (c.1853G>T)?

AlphaMissense predicts ambiguous (score 0.4561) — an in-silico prediction, not a clinical call.

CD22 p.Ser618Ile

c.1853G>T · VCV3264777

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4561 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4561	ambiguous
REVEL	0.104	moderately benign-leaning
SaProt	LLR -13.42	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.3, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 15 kb · p 7.1e-05 · regional, not allelic
Overall
CADD	22.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CD22
Protein: p.Ser618Ile
Coding: c.1853G>T
MANE Select: NM_001771
Type: single nucleotide variant
Location: chr19:35341783 (GRCh38)
Gene constraint: LOEUF 0.639 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.33 · 7 PDB
Residue 618: a β-strand; the ig-like c2-type 6 domain; a disulfide bond

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-ser618ile (accessed [today's date]).

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