Is CD22 p.Val217Met (c.649G>A) pathogenic?

CD22 p.Val217Met (c.649G>A) is classified Uncertain significance in CD22 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-25). AlphaMissense: likely benign (0.1855); Ultra-rare (popmax 0.0461%, sas).

How common is CD22 p.Val217Met (c.649G>A) in the general population?

CD22 p.Val217Met (c.649G>A) is ultra-rare (popmax 0.0461%, sas) (gnomAD).

What do computational predictors say about CD22 p.Val217Met (c.649G>A)?

AlphaMissense predicts likely benign (score 0.1855) — an in-silico prediction, not a clinical call.

CD22 p.Val217Met

c.649G>A · rs577316886 · VCV3140451

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1855 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0461%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1855	likely benign
REVEL	0.141	moderately benign-leaning
SaProt	LLR -6.40	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 0.25	GERP -4.1, phastCons 0.009
Regional constraint	o/e 0.88	unconstrained · MANE · 15 kb · p 7.1e-05 · regional, not allelic
Overall
CADD	12.17	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 0.0461% South Asian · 42/91,090 alleles

Filtering AF 0.035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0311%

Overall 0.00291% 47/1,614,218 alleles · ultra-rare exomes 45/1,461,890 · genomes 2/152,328 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0461%	2,169
Remaining individualsnot grpmax-eligible	0.008%	12,502

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.Val217Met
Coding: c.649G>A
MANE Select: NM_001771
dbSNP: rs577316886
Type: single nucleotide variant
Location: chr19:35336272 (GRCh38)
Gene constraint: LOEUF 0.639 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.33 · 7 PDB
Residue 217: the ig-like c2-type 1 domain; a β-strand

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-val217met (accessed [today's date]).

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