DHFR p.Ser77=
c.231C>T · rs1748867913 · VCV2113386
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.5e-05%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.64 | GERP -1.1, phastCons 0.94 |
| Overall | ||
| CADD | 6.403 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.5e-05%
European (non-Finnish) · 1/1,176,022 alleles
Overall
6.88e-05%
1/1,454,058 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.Ser77=
- Coding
- c.231C>T
- MANE Select
- NM_000791
- dbSNP
- rs1748867913
- Type
- single nucleotide variant
- Location
- chr5:80649400 (GRCh38)
- Gene constraint
- LOEUF 0.994 · pLI 0.06 (gnomAD)
- Structure
- AlphaFold pLDDT 96.32 · 89 PDB
- Residue 77
- the dhfr domain; a binding site
Similar variants
- MSH3 p.Pro77Arg Uncertain significance ★★ ⚠ same residue
- MSH3 p.Pro77Gln Uncertain significance ★★ ⚠ same residue
- MSH3 p.Pro77Ser Uncertain significance ★★ ⚠ same residue
- MSH3 p.Pro77= Likely benign ★ same residue
- MSH3 p.Pro77_His78insPro Uncertain significance ★★ same residue
- MSH3 p.Pro77_His78insGlnLeuProPro Uncertain significance ★ same residue
- MSH3 p.Pro77del Uncertain significance ★ same residue
- DHFR c.-476C>G 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-ser77 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown