Is MKKS p.Pro39= (c.117C>T) pathogenic?

MKKS p.Pro39= (c.117C>T) is classified Benign in MKKS (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-02-04). Common (popmax 33.3%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Bardet-Biedl syndrome.

What condition is associated with MKKS p.Pro39= (c.117C>T)?

MKKS p.Pro39= (c.117C>T) is associated with Bardet-Biedl syndrome, McKusick-Kaufman syndrome, Bardet-Biedl syndrome 6 (ClinVar).

How is Bardet-Biedl syndrome inherited?

Typically Autosomal recessive, Oligogenic (Orphanet). A genetic counselor can assess individual risk for a family.

MKKS p.Pro39=

Q: How common is MKKS p.Pro39= (c.117C>T) in the general population?

MKKS p.Pro39= (c.117C>T) is common (popmax 33.3%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.117C>T · rs16991547 · VCV21669

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Common

common (popmax 33.3%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Bardet-Biedl 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 -0.56	GERP -4.2
Overall
CADD	0.84	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 33.3% African / African-American · 24,978/74,908 alleles

Filtering AF 33% ClinGen BA1/BS1 input FAF95, joint · FAF99 32.9%

Overall 13.4% 215,765/1,612,488 alleles · common exomes 187,710/1,460,422 · genomes 28,055/152,066 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	33.3%	3
East Asian	24.8%	4
South Asian	24%	4
Remaining individualsnot grpmax-eligible	14.3%	7
Middle Eastern	14%	7
Admixed American	13.2%	8
Finnishnot grpmax-eligible	11.6%	9
European (non-Finnish)	11%	9
Ashkenazi Jewishnot grpmax-eligible	10.4%	10
Amishnot grpmax-eligible	2.63%	38

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.Pro39=
Coding: c.117C>T
MANE Select: NM_170784
dbSNP: rs16991547
Type: single nucleotide variant
Location: chr20:10413398 (GRCh38)
Gene constraint: LOEUF 1.112 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 89.05

Full MKKS gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Bardet-Biedl syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: McKusick-Kaufman syndrome Bardet-Biedl syndrome 6

For Bardet-Biedl syndrome (Orphanet):

Inheritance: Autosomal recessive, Oligogenic
Onset: Antenatal, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Specific population)

Similar variants

MKKS p.Pro39Leu Conflicting classifications of pathogenicity ★ ⚠ 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
MKKS p.His84Tyr 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-pro39 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown