MLC1 p.Asp31=
c.93C>T · rs199625892 · VCV289952
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0253%, afr)
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 0.6 | GERP -0.3, phastCons 0.055 |
| Overall | ||
| CADD | 7.322 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0253%
African / African-American · 19/75,068 alleles
Filtering AF
0.0165%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0137%
Overall
0.0026%
42/1,614,018 alleles · ultra-rare
exomes 28/1,461,646 · genomes 14/152,372 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0253% | 3,951 |
| South Asian | 0.011% | 9,109 |
| East Asian | 0.00891% | 11,222 |
| European (non-Finnish) | 0.000763% | 131,117 |
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.Asp31=
- Coding
- c.93C>T
- MANE Select
- NM_015166
- dbSNP
- rs199625892
- Type
- single nucleotide variant
- Location
- chr22:50084810 (GRCh38)
- Gene constraint
- LOEUF 1.038 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 71.29
- Residue 31
- the 'disordered' region
Similar variants
- MLC1 p.Asp31fs Likely pathogenic ★ 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-asp31 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown