GFM1 p.Val125Met
c.373G>A · rs200923387 · VCV343923
Computational evidence
| Protein change | ||
| AlphaMissense | 0.8969 | likely pathogenic |
|---|---|---|
| REVEL | 0.81 | moderately pathogenic-leaning |
| SaProt | LLR -11.72 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 2.1, phastCons 1 |
| Regional constraint | o/e 0.93 | unconstrained · MANE · 47 kb · p 0.033 · regional, not allelic |
| Overall | ||
| CADD | 31.0 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Ashkenazi Jewishnot grpmax-eligible | 0.679% | 147 |
| Remaining individualsnot grpmax-eligible | 0.048% | 2,081 |
| Admixed Americangrpmax | 0.025% | 3,992 |
| European (non-Finnish) | 0.00263% | 38,051 |
| African / African-American | 0.00133% | 74,936 |
Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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
- GFM1
- Protein
- p.Val125Met
- Coding
- c.373G>A
- MANE Select
- NM_024996
- dbSNP
- rs200923387
- Type
- single nucleotide variant
- Location
- chr3:158646748 (GRCh38)
- Gene constraint
- LOEUF 0.829 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 82.36 · 5 PDB
- Residue 125
- the tr-type g domain; a β-strand
Disease context
hepatoencephalopathy due to combined oxidative phosphorylation defect type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1 (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Neonatal
Similar variants
- GFM1 c.1380+1G>A Likely pathogenic ★★ same condition
- GFM1 c.1380+1G>T Likely pathogenic ★★ same condition
- GFM1 c.1764+2T>C Likely pathogenic ★★ same condition
- GFM1 c.1765-2A>G Pathogenic/Likely pathogenic ★★ same condition
- GFM1 c.1910-1G>A Likely pathogenic ★★ same condition
- GFM1 c.1910-2A>T Likely pathogenic ★★ same condition
- GFM1 c.2070+1G>A Likely pathogenic ★★ same condition
- GFM1 c.368-2A>G Likely pathogenic ★★ same condition
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/gfm1-p-val125met (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown