MLC1 p.Arg42=
c.126A>G · rs1005823986 · VCV1094904
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00333%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.039 | GERP -0.88, phastCons 0.59 |
| Overall | ||
| CADD | 12.03 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00333%
Admixed American · 2/60,006 alleles
Filtering AF
0.000763%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000605%
Overall
0.00118%
19/1,613,980 alleles · very rare
exomes 18/1,461,786 · genomes 1/152,194 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00333% | 30,003 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,243 |
| European (non-Finnish) | 0.00127% | 78,670 |
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
- MLC1
- Protein
- p.Arg42=
- Coding
- c.126A>G
- MANE Select
- NM_015166
- dbSNP
- rs1005823986
- Type
- single nucleotide variant
- Location
- chr22:50084777 (GRCh38)
- Gene constraint
- LOEUF 1.038 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 71.29
Similar variants
- MLC1 p.Arg42Thr Uncertain significance ★ ⚠ same residue
- MLC1 c.1059+1G>A Likely pathogenic ★★ same type
- MLC1 c.321+1G>A Likely pathogenic ★★ same type
- MLC1 c.321+2T>C Likely pathogenic ★★ same type
- MLC1 c.321+2T>G Likely pathogenic ★★ same type
- MLC1 c.423+1G>A Pathogenic/Likely pathogenic ★★ same type
- MLC1 c.423+1G>T Pathogenic/Likely pathogenic ★★ same type
- MLC1 c.525+1G>A 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/mlc1-p-arg42 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown