Is ADAM17 p.Pro20= (c.60T>G) pathogenic?

ADAM17 p.Pro20= (c.60T>G) is classified Likely benign in ADAM17 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-25). Very rare (popmax 0.00899%, eas); Associated with inflammatory skin and bowel disease, neonatal, 1.

What condition is associated with ADAM17 p.Pro20= (c.60T>G)?

ADAM17 p.Pro20= (c.60T>G) is associated with inflammatory skin and bowel disease, neonatal, 1 (ClinVar).

How common is ADAM17 p.Pro20= (c.60T>G) in the general population?

ADAM17 p.Pro20= (c.60T>G) is very rare (popmax 0.00899%, eas) (gnomAD).

ADAM17 p.Pro20=

Q: How is Neonatal erythroderma-autoinflammation-inflammatory bowel disease syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.60T>G · rs1442391766 · VCV2985490

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00899%, eas)

Conditions

inflammatory skin and bowel disease, neonatal, 1

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 0.66	GERP 0.65, phastCons 0.97
Overall
CADD	11.45	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00899% East Asian · 4/44,472 alleles

Filtering AF 0.003% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00181%

Overall 0.000561% 9/1,603,842 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00899%	11,118
Remaining individualsnot grpmax-eligible	0.00484%	20,663
Admixed American	0.0017%	58,666
European (non-Finnish)	8.51e-05%	1,175,244

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: ADAM17
Protein: p.Pro20=
Coding: c.60T>G
MANE Select: NM_003183
dbSNP: rs1442391766
Type: single nucleotide variant
Location: chr2:9555546 (GRCh38)
Gene constraint: LOEUF 0.565 · pLI 0.10 (gnomAD)
Structure: AlphaFold pLDDT 72.72 · 33 PDB

Full ADAM17 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

inflammatory skin and bowel disease, neonatal, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Neonatal erythroderma-autoinflammation-inflammatory bowel disease syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ADAM17 p.Pro20Arg Uncertain significance ★ ⚠ same residue
ADAM17 p.Arg651Ter Pathogenic/Likely pathogenic ★★ same condition
ADAM17 p.Ala742Thr Uncertain significance ★★ ⚠ same condition
ADAM17 p.Ala806Pro Uncertain significance ★★ ⚠ same condition
ADAM17 p.Ala806Ser Uncertain significance ★★ ⚠ same condition
ADAM17 p.Arg132Lys Uncertain significance ★★ ⚠ same condition
ADAM17 p.Arg177His Uncertain significance ★★ ⚠ same condition
ADAM17 p.Arg738Cys 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/adam17-p-pro20 (accessed [today's date]).

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