MKKS p.Pro522=
c.1566A>T · VCV4788733
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000169%, nfe)
Conditions
2
McKusick-Kaufman syndrome
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 -2 | GERP -4.2 |
| Overall | ||
| CADD | 1.205 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000169%
European (non-Finnish) · 2/1,180,034 alleles
Filtering AF
2.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000124%
2/1,614,192 alleles · very rare
exomes 2/1,461,884 · genomes 0/152,308 · joint denominator
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
- MKKS
- Protein
- p.Pro522=
- Coding
- c.1566A>T
- MANE Select
- NM_170784
- Type
- single nucleotide variant
- Location
- chr20:10405394 (GRCh38)
- Gene constraint
- LOEUF 1.112 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 89.05
- Residue 522
- a UniProt-annotated variant site (in bbs6)
Similar variants
- MKKS c.986-1G>A Pathogenic ★★ same condition
- MKKS p.Arg139Ter Pathogenic/Likely pathogenic ★★ same condition
- MKKS p.Gln391Ter Pathogenic/Likely pathogenic ★★ same condition
- MKKS p.Gln59Ter Pathogenic/Likely pathogenic ★★ same condition
- MKKS p.Gly345Glu Pathogenic/Likely pathogenic ★★ same condition
- MKKS p.Gly52Asp Pathogenic/Likely pathogenic ★★ same condition
- MKKS p.His84Tyr Pathogenic/Likely pathogenic ★★ ⚠ same condition
- MKKS p.Leu74Ter 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/mkks-p-pro522 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown