MTR p.Arg61=
c.181A>C · rs886046217 · VCV296549
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00133%, afr)
Conditions
2
Disorders of Intracellular Cobalamin Metabolism
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 3.8 | GERP 0.31, phastCons 1 |
| Overall | ||
| CADD | 10.44 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00133%
African / African-American · 1/75,064 alleles
Filtering AF
0.000688%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000539%
Overall
0.000929%
15/1,614,224 alleles · very rare
exomes 15/1,461,866 · genomes 0/152,358 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00133% | 75,064 |
| European (non-Finnish) | 0.00119% | 84,287 |
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
- MTR
- Protein
- p.Arg61=
- Coding
- c.181A>C
- MANE Select
- NM_000254
- dbSNP
- rs886046217
- Type
- single nucleotide variant
- Location
- chr1:236803574 (GRCh38)
- Gene constraint
- LOEUF 0.625 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 87.60 · 9 PDB
- Residue 61
- the hcy-binding domain; a UniProt-annotated variant site (sequence variant)
Similar variants
- MTR c.1812+1G>A Likely pathogenic ★★ same condition
- MTR c.2474-1G>C Pathogenic ★★ same condition
- MTR c.2595-2A>G Likely pathogenic ★★ same condition
- MTR c.340-166A>G Pathogenic/Likely pathogenic ★★ same condition
- MTR c.609+1088G>A Pathogenic ★★ same condition
- MTR c.866-2A>C Pathogenic/Likely pathogenic ★★ same condition
- MTR p.Arg1147Ter Pathogenic ★★ same condition
- MTR p.Arg585Ter Pathogenic/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/mtr-p-arg61 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown