SHMT2 p.Ile264=
c.792T>A · VCV4917381
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.054 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.13 | GERP -4.8, phastCons 0.46 |
| Overall | ||
| CADD | 5.915 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/59,986 alleles
Overall
0.000186%
3/1,613,516 alleles · very rare
exomes 2/1,461,298 · genomes 1/152,218 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 59,986 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,462 |
| European (non-Finnish) | 8.48e-05% | 1,179,592 |
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
- SHMT2
- Protein
- p.Ile264=
- Coding
- c.792T>A
- MANE Select
- NM_005412
- Type
- single nucleotide variant
- Location
- chr12:57232778 (GRCh38)
- Gene constraint
- LOEUF 0.794 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.24 · 33 PDB
Similar variants
- SHMT2 p.Arg230His Uncertain significance ★★ same type
- SHMT2 p.Arg25Gln Uncertain significance ★★ ⚠ same type
- SHMT2 p.Arg359Trp Uncertain significance ★★ ⚠ same type
- SHMT2 p.Arg434Ter Uncertain significance ★★ same type
- SHMT2 p.Arg442Trp Uncertain significance ★★ ⚠ same type
- SHMT2 p.Arg488Trp Uncertain significance ★★ ⚠ same type
- SHMT2 p.Arg82Leu Uncertain significance ★★ ⚠ same type
- SHMT2 p.Asp378His 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/shmt2-p-ile264 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown