MLC1 p.Pro34=
c.102G>A · rs778840124 · VCV764813
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00636%, nfe)
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 -0.04 | GERP -3 |
| Overall | ||
| CADD | 4.891 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00636%
European (non-Finnish) · 75/1,180,060 alleles
Filtering AF
0.00519%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00473%
Overall
0.00477%
77/1,613,932 alleles · very rare
exomes 71/1,461,702 · genomes 6/152,230 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00636% | 15,734 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,488 |
| African / African-American | 0.00133% | 74,938 |
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.Pro34=
- Coding
- c.102G>A
- MANE Select
- NM_015166
- dbSNP
- rs778840124
- Type
- single nucleotide variant
- Location
- chr22:50084801 (GRCh38)
- Gene constraint
- LOEUF 1.038 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 71.29
- Residue 34
- the 'disordered' region
Similar variants
- MLC1 p.Pro34Leu 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-pro34 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown