SETD2 p.Phe144Val
c.430T>G · VCV4538129
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.9435 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
1/2 damaging
AlphaMissense, SaProt · REVEL indeterminate
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9435 | likely pathogenic |
|---|---|---|
| REVEL | 0.604 | indeterminate |
| SaProt | LLR -5.32 | tolerated |
| ⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 2.3, phastCons 1 |
| Regional constraint | o/e 0.89 | unconstrained · MANE · 40 kb · p 0.036 · regional, not allelic |
| Overall | ||
| CADD | 24.1 | 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.
Variant & gene context
- Gene
- SETD2
- Protein
- p.Phe144Val
- Coding
- c.430T>G
- MANE Select
- NM_014159
- Type
- single nucleotide variant
- Location
- chr3:47124206 (GRCh38)
- Gene constraint
- LOEUF 0.176 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 43.81 · 43 PDB
- Residue 144
- a UniProt-annotated variant site (in aml; uncertain significance; somatic mutation)
Similar variants
- SETD2 p.Phe144Ile Uncertain significance ★ ⚠ same residue
- SETD2 p.Arg1598Ter Pathogenic/Likely pathogenic ★★ same type
- SETD2 p.Arg1740Gln Pathogenic ★★ ⚠ same type
- SETD2 p.Arg1740Trp Pathogenic/Likely pathogenic ★★ same type
- SETD2 p.Arg441Ter Likely pathogenic ★★ same type
- SETD2 p.Glu1718Lys Likely pathogenic ★★ ⚠ same type
- SETD2 c.4715+5G>A Uncertain significance ★★ same type
- SETD2 p.Ala1121Thr 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/setd2-p-phe144val (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown