Is MKKS p.Ser249= (c.747C>T) pathogenic?

MKKS p.Ser249= (c.747C>T) is classified Likely benign in MKKS (ClinVar, Single submitter, 2 submitters; last evaluated 2024-03-17). Very rare (popmax 0.00517%, nfe); Associated with Bardet-Biedl syndrome.

What condition is associated with MKKS p.Ser249= (c.747C>T)?

MKKS p.Ser249= (c.747C>T) is associated with Bardet-Biedl syndrome, McKusick-Kaufman syndrome (ClinVar).

How common is MKKS p.Ser249= (c.747C>T) in the general population?

MKKS p.Ser249= (c.747C>T) is very rare (popmax 0.00517%, nfe) (gnomAD).

How is Bardet-Biedl syndrome inherited?

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

MKKS p.Ser249=

c.747C>T · rs187543885 · VCV1649948

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00517%, nfe)

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 -6	GERP -4.2
Overall
CADD	0.797	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00517% European (non-Finnish) · 61/1,180,018 alleles

Filtering AF 0.0041% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00372%

Overall 0.00421% 68/1,614,116 alleles · very rare exomes 66/1,461,878 · genomes 2/152,238 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00517%	19,345
Remaining individualsnot grpmax-eligible	0.0048%	20,837
East Asian	0.00223%	44,870
South Asian	0.0022%	45,542
Admixed American	0.00167%	60,008

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.Ser249=
Coding: c.747C>T
MANE Select: NM_170784
dbSNP: rs187543885
Type: single nucleotide variant
Location: chr20:10412768 (GRCh38)
Gene constraint: LOEUF 1.112 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 89.05
Residue 249: the 'substrate-binding apical domain' region; a UniProt-annotated variant site (in bbs6)

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

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.Ser249Phe 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
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-ser249 (accessed [today's date]).

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