DHFR p.Lys55=
c.165G>A · VCV4770650
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00017%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.23 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.2 | GERP -0.78, phastCons 0.17 |
| Overall | ||
| CADD | 4.222 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00017%
European (non-Finnish) · 2/1,179,298 alleles
Filtering AF
2.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000137%
2/1,460,762 alleles · very rare
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
- DHFR
- Protein
- p.Lys55=
- Coding
- c.165G>A
- MANE Select
- NM_000791
- Type
- single nucleotide variant
- Location
- chr5:80649466 (GRCh38)
- Gene constraint
- LOEUF 0.994 · pLI 0.06 (gnomAD)
- Structure
- AlphaFold pLDDT 96.32 · 89 PDB
- Residue 55
- the dhfr domain; an α-helix; a binding site
Similar variants
- MSH3 p.Ala55= Likely benign ★★ same residue
- MSH3 p.Ala55_Ala56insGluAlaAlaAlaAlaAla Uncertain significance ★ same residue
- MSH3 p.Ala55_Ala56insGlyAlaAla Conflicting classifications of pathogenicity ★ same residue
- DHFR c.-476C>G Likely pathogenic ★★ same type
- MSH3 c.237+1G>A Likely pathogenic ★★ same type
- MSH3 c.237+2T>C Pathogenic/Likely pathogenic ★★ same type
- MSH3 p.Arg26Ter Pathogenic/Likely pathogenic ★★ same type
- MSH3 p.Gln46Ter Pathogenic/Likely 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/dhfr-p-lys55 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown