Is ADAM17 p.Asp760= (c.2280C>T) pathogenic?

ADAM17 p.Asp760= (c.2280C>T) is classified Likely benign in ADAM17 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-06-29). Ultra-rare (popmax 0.0329%, mid); Associated with inflammatory skin and bowel disease, neonatal, 1.

What condition is associated with ADAM17 p.Asp760= (c.2280C>T)?

ADAM17 p.Asp760= (c.2280C>T) is associated with inflammatory skin and bowel disease, neonatal, 1 (ClinVar).

How common is ADAM17 p.Asp760= (c.2280C>T) in the general population?

ADAM17 p.Asp760= (c.2280C>T) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

ADAM17 p.Asp760=

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.2280C>T · rs371018540 · VCV732719

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

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 3.7	GERP 0.4, phastCons 1
Overall
CADD	7.693	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,084 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0098%

Overall 0.00942% 152/1,614,066 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,042
European (non-Finnish)	0.012%	8,310
Remaining individualsnot grpmax-eligible	0.0048%	20,829
South Asian	0.00329%	30,362
African / African-American	0.00267%	37,459

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.Asp760=
Coding: c.2280C>T
MANE Select: NM_003183
dbSNP: rs371018540
Type: single nucleotide variant
Location: chr2:9490372 (GRCh38)
Gene constraint: LOEUF 0.565 · pLI 0.10 (gnomAD)
Structure: AlphaFold pLDDT 72.72 · 33 PDB
Residue 760: the 'disordered' region

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.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
ADAM17 p.Arg813His 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-asp760 (accessed [today's date]).

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