MKKS p.Arg281=
c.843G>A · rs1460870072 · VCV2953958
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00133%, afr)
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 0.12 | GERP -0.68, phastCons 0.003 |
| Overall | ||
| CADD | 7.396 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00133%
African / African-American · 1/75,030 alleles
Filtering AF
2.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000186%
3/1,614,124 alleles · very rare
exomes 3/1,461,852 · genomes 0/152,272 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00133% | 75,030 |
| European (non-Finnish) | 0.000169% | 590,012 |
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.Arg281=
- Coding
- c.843G>A
- MANE Select
- NM_170784
- dbSNP
- rs1460870072
- Type
- single nucleotide variant
- Location
- chr20:10412672 (GRCh38)
- Gene constraint
- LOEUF 1.112 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 89.05
- Residue 281
- the 'substrate-binding apical domain' region; a UniProt-annotated variant site (in bbs6)
Similar variants
- MKKS p.Arg281Ser Uncertain significance ★ ⚠ same residue
- MKKS p.Arg281Thr Uncertain significance ★ ⚠ same residue
- 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
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-arg281 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown