Is ADAM22 p.Pro882Ser (c.2644C>T) pathogenic?

ADAM22 p.Pro882Ser (c.2644C>T) is classified Uncertain significance in ADAM22 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-30). AlphaMissense: ambiguous (0.4207); Very rare (popmax 0.00229%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ADAM22 p.Pro882Ser (c.2644C>T)?

ADAM22 p.Pro882Ser (c.2644C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ADAM22 p.Pro882Ser (c.2644C>T) in the general population?

ADAM22 p.Pro882Ser (c.2644C>T) is very rare (popmax 0.00229%, nfe) (gnomAD).

What do computational predictors say about ADAM22 p.Pro882Ser (c.2644C>T)?

AlphaMissense predicts ambiguous (score 0.4207) — an in-silico prediction, not a clinical call.

ADAM22 p.Pro882Ser

c.2644C>T · VCV3487311

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4207 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00229%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4207	ambiguous
REVEL	0.179	moderately benign-leaning
SaProt	LLR -5.14	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.31	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 7.7	GERP 4.1, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 80 kb · p 2.1e-12 · regional, not allelic
Overall
CADD	27.6	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P853S vs ClinVar P882S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00229% European (non-Finnish) · 27/1,179,728 alleles

Filtering AF 0.00157% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00134%

Overall 0.00185% 27/1,461,476 alleles · very rare

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: ADAM22
Protein: p.Pro882Ser
Coding: c.2644C>T
MANE Select: NM_001324418
Type: single nucleotide variant
Location: chr7:88182005 (GRCh38)
Gene constraint: LOEUF 0.518 · pLI 0.55 (gnomAD)
Structure: AlphaFold pLDDT 73.17 · 10 PDB
Residue 882: the 'disordered' region

Full ADAM22 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ADAM22 p.Arg513Ser Uncertain significance ★★ ⚠ same condition
ADAM22 p.Gly164Arg Uncertain significance ★★ ⚠ same condition
ADAM22 p.Pro525Thr Uncertain significance ★★ ⚠ same condition
ADAM22 p.Thr713Ser Uncertain significance ★★ ⚠ same condition
ADAM22 p.Tyr57Cys Uncertain significance ★★ ⚠ same condition
ADAM22 p.Val259Ile Uncertain significance ★★ ⚠ same condition
ADAM22 p.Ala524= Likely benign ★★ same condition
ADAM22 c.1617+3A>G Uncertain significance ★ same condition

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/adam22-p-pro882ser (accessed [today's date]).

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