Is ADAM22 p.Cys154= (c.462C>T) pathogenic?

ADAM22 p.Cys154= (c.462C>T) is classified Likely benign in ADAM22 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-01). Very rare (popmax 0.000678%, nfe); Associated with ADAM22-related disorder.

What condition is associated with ADAM22 p.Cys154= (c.462C>T)?

ADAM22 p.Cys154= (c.462C>T) is associated with ADAM22-related disorder (ClinVar).

How common is ADAM22 p.Cys154= (c.462C>T) in the general population?

ADAM22 p.Cys154= (c.462C>T) is very rare (popmax 0.000678%, nfe) (gnomAD).

ADAM22 p.Cys154=

c.462C>T · rs1258927537 · VCV3035880

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Conditions

ADAM22-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 5.2, phastCons 1
Overall
CADD	12.08	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000678% European (non-Finnish) · 8/1,179,614 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000496% 8/1,613,062 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.Cys154=
Coding: c.462C>T
MANE Select: NM_001324418
dbSNP: rs1258927537
Type: single nucleotide variant
Location: chr7:88108247 (GRCh38)
Gene constraint: LOEUF 0.518 · pLI 0.55 (gnomAD)
Structure: AlphaFold pLDDT 73.17 · 10 PDB

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

Disease context

ADAM22-related disorder

Similar variants

ADAM22 p.Arg954Ter Pathogenic ★ same condition
ADAM22 c.1618-5T>C Likely benign same condition
ADAM22 c.826-7A>G Likely benign same condition
ADAM22 p.Glu128Lys Benign ⚠ same condition
ADAM22 p.Leu55Phe Benign ⚠ same condition
ADAM22 p.Thr589= Likely benign same condition
ADAM22 p.Tyr760= Likely benign same condition
ADAM22 p.Ile752fs Likely pathogenic 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-cys154 (accessed [today's date]).

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