SHMT2 p.Tyr151=
c.453C>T · VCV3778010
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0192%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.118 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -1.3 | GERP -4.5 |
| Overall | ||
| CADD | 2.613 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0192%
European (non-Finnish) · 226/1,179,984 alleles
Filtering AF
0.0171%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0162%
Overall
0.0149%
241/1,613,956 alleles · ultra-rare
exomes 224/1,461,730 · genomes 17/152,226 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0192% | 5,221 |
| Remaining individualsnot grpmax-eligible | 0.0144% | 6,943 |
| African / African-American | 0.00667% | 14,986 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,596 |
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.Tyr151=
- Coding
- c.453C>T
- MANE Select
- NM_005412
- Type
- single nucleotide variant
- Location
- chr12:57231854 (GRCh38)
- Gene constraint
- LOEUF 0.794 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.24 · 33 PDB
- Residue 151
- an α-helix
Similar variants
- SHMT2 p.Tyr151Cys Uncertain significance ★ ⚠ same residue
- 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
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-tyr151 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown