KIT p.Asp816His
c.2446G>C · rs121913506 · VCV13863
Pathogenic
Multiple submitters
Classification
Pathogenic
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
AlphaMissense
likely pathogenic
0.9993 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
3/3 damaging
AlphaMissense, REVEL, SaProt
Conditions
2
dysgerminoma
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9993 | likely pathogenic ✓ concordant with ClinVar · top 4% in KIT |
|---|---|---|
| REVEL | 0.742 | pathogenic-leaning |
| SaProt | LLR -13.02 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 2.6, phastCons 1 |
| Regional constraint | o/e 0.46 | unconstrained · MANE · 4,810 bp · p 2.2e-10 · regional, not allelic |
| Overall | ||
| CADD | 28.0 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Cancer therapy — CIViC
| Disease | Therapies | Level | Significance |
|---|---|---|---|
| Gastrointestinal Stromal Tumor | Imatinib | C | Resistance |
| Gastrointestinal Stromal Tumor | Sunitinib | D | Sensitivity/Response |
| Gastrointestinal Stromal Tumor | Regorafenib | D | Resistance |
| Chronic Myeloid Leukemia | Bosutinib | D | Sensitivity/Response |
| Chronic Myeloid Leukemia | Dasatinib | D | Sensitivity/Response |
| Acute Myeloid Leukemia | Imatinib Mesylate | D | Resistance |
| Gastrointestinal Stromal Tumor | Ponatinib | D | Sensitivity/Response |
Variant & gene context
- Gene
- KIT
- Protein
- p.Asp816His
- Coding
- c.2446G>C
- MANE Select
- NM_000222
- dbSNP
- rs121913506
- Type
- single nucleotide variant
- Location
- chr4:54733154 (GRCh38)
- Gene constraint
- LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 78.52 · 65 PDB
- Residue 816
- the protein kinase domain; a UniProt-annotated variant site (in mastc; sporadic case; somatic mutation; constitutively activated and is much more rapidly autophosphorylated than wild type; requires 2 nucleotide substitutions); a UniProt-annotated variant site (in a testicular tumor; seminoma; somatic mutation; constitutively activated); a UniProt-annotated variant site (in mastc; somatic mutation; constitutively activated; requires 2 nucleotide substitutions); a UniProt-annotated variant site (in mastsys, mastc and mast cell leukemia; somatic mutation; constitutively activated; loss of interaction with mpdz); a UniProt-annotated variant site (in mastsys and mastc; also found in acute myeloid leukemia and a germ cell tumor of the testis; somatic mutation; constitutively activated)
Similar variants
- KIT p.Asp816Val Conflicting classifications of pathogenicity ★ ⚠ same residue
- KIT p.Asp816Asn Uncertain significance ★★ ⚠ same residue
- KIT p.Asp816= Conflicting classifications of pathogenicity ★ same residue
- KIT p.Asp816Gly Uncertain significance ★ ⚠ same residue
- KIT p.Asp816Tyr Uncertain significance ★ ⚠ same residue
- KIT c.67+5G>T Uncertain significance ★★ same condition
- KIT p.Arg634Trp Uncertain significance ★★ ⚠ same condition
- KIT p.Asn326Lys 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/kit-p-asp816his (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown