ADAM17 p.Phe664=
c.1992T>C · rs1185937477 · VCV3057915
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00203%, nfe)
Conditions
1
ADAM17-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 -6 | GERP -4.2 |
| Overall | ||
| CADD | 0.173 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00203%
European (non-Finnish) · 24/1,179,374 alleles
Filtering AF
0.00138%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00116%
Overall
0.00178%
26/1,460,938 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00203% | 49,141 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,484 |
| South Asian | 0.0011% | 90,994 |
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.Phe664=
- Coding
- c.1992T>C
- MANE Select
- NM_003183
- dbSNP
- rs1185937477
- Type
- single nucleotide variant
- Location
- chr2:9493748 (GRCh38)
- Gene constraint
- LOEUF 0.565 · pLI 0.10 (gnomAD)
- Structure
- AlphaFold pLDDT 72.72 · 33 PDB
- Residue 664
- an α-helix; the 'crambin-like' region
Disease context
ADAM17-related disorder
Similar variants
- ADAM17 p.Gln531Ter Likely pathogenic ★ same condition
- ADAM17 c.958-9C>G Likely benign same condition
- ADAM17 p.Arg651Ter Pathogenic/Likely pathogenic ★★ same type
- ADAM17 p.Ala742Thr Uncertain significance ★★ ⚠ same type
- ADAM17 p.Ala806Pro Uncertain significance ★★ ⚠ same type
- ADAM17 p.Ala806Ser Uncertain significance ★★ ⚠ same type
- ADAM17 p.Arg132Lys Uncertain significance ★★ ⚠ same type
- ADAM17 p.Arg177His 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/adam17-p-phe664 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown