MLC1 p.Phe232=
c.696C>T · rs747751986 · VCV1143784
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0275%, sas)
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 7.2 | GERP 1.6, phastCons 1 |
| Overall | ||
| CADD | 12.74 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0275%
South Asian · 25/90,972 alleles
Filtering AF
0.019%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0163%
Overall
0.00167%
27/1,613,490 alleles · ultra-rare
exomes 26/1,461,274 · genomes 1/152,216 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0275% | 3,639 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,232 |
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.Phe232=
- Coding
- c.696C>T
- MANE Select
- NM_015166
- dbSNP
- rs747751986
- Type
- single nucleotide variant
- Location
- chr22:50074234 (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 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
- MLC1 c.597+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-phe232 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown