SETD2 p.Ser838del
c.2511TAG[1] · VCV3343168
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000254%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.1 | GERP 1.1, phastCons 1 |
| Overall | ||
| CADD | 11.99 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000254%
European (non-Finnish) · 3/1,179,978 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000186%
3/1,613,892 alleles · very rare
exomes 2/1,461,652 · genomes 1/152,240 · joint denominator
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
- SETD2
- Protein
- p.Ser838del
- Coding
- c.2511TAG[1]
- MANE Select
- NM_014159
- Type
- Microsatellite
- Location
- chr3:47122120 (GRCh38)
- Gene constraint
- LOEUF 0.176 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 43.81 · 43 PDB
- Residue 838
- a UniProt-annotated variant site (in aml; uncertain significance; somatic mutation); a UniProt-annotated variant site (in all; uncertain significance; somatic mutation)
Similar variants
- SETD2 c.4457_4460delAGAA Pathogenic ★★ same type
- SETD2 p.Asp429_Ser430insTer Pathogenic/Likely pathogenic ★★ same type
- SETD2 p.Val768fs Pathogenic/Likely pathogenic ★★ same type
- SETD2 c.4918-78AC[17] Benign/Likely benign ★★ same type
- SETD2 p.Asn806_Ser807insTer Pathogenic ★ same type
- SETD2 p.Asp1841fs Likely pathogenic ★ same type
- SETD2 p.Asp2064fs Likely pathogenic ★ same type
- SETD2 p.Asp350fs Pathogenic ★ 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/setd2-p-ser838del (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown