Is CD22 p.Pro812Thr (c.2434C>A) pathogenic?

CD22 p.Pro812Thr (c.2434C>A) is classified Uncertain significance in CD22 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-17). AlphaMissense: likely benign (0.0888); Rare (popmax 0.562%, mid).

How common is CD22 p.Pro812Thr (c.2434C>A) in the general population?

CD22 p.Pro812Thr (c.2434C>A) is rare (popmax 0.562%, mid) (gnomAD).

What do computational predictors say about CD22 p.Pro812Thr (c.2434C>A)?

AlphaMissense predicts likely benign (score 0.0888) — an in-silico prediction, not a clinical call.

CD22 p.Pro812Thr

c.2434C>A · VCV3998111

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0888 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.562%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0888	likely benign
REVEL	0.246	benign-leaning
SaProt	LLR -7.20	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 0.32	GERP 0.56
Regional constraint	o/e 0.88	unconstrained · MANE · 15 kb · p 7.1e-05 · regional, not allelic
Overall
CADD	17.63	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.562% Middle Eastern · 34/6,052 alleles

Filtering AF 0.413% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.362%

Overall 0.00268% 43/1,603,880 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.562%	178
Remaining individualsnot grpmax-eligible	0.00483%	20,703
South Asian	0.00448%	22,345
African / African-American	0.00267%	37,451

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.Pro812Thr
Coding: c.2434C>A
MANE Select: NM_001771
Type: single nucleotide variant
Location: chr19:35346587 (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.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-pro812thr (accessed [today's date]).

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