Is MKKS p.Val565= (c.1695T>C) pathogenic?

MKKS p.Val565= (c.1695T>C) is classified Likely benign in MKKS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-10-05). Ultra-rare (popmax 0.0107%, afr); Associated with Bardet-Biedl syndrome.

What condition is associated with MKKS p.Val565= (c.1695T>C)?

MKKS p.Val565= (c.1695T>C) is associated with Bardet-Biedl syndrome, McKusick-Kaufman syndrome, Bardet-Biedl syndrome 6 (ClinVar).

How common is MKKS p.Val565= (c.1695T>C) in the general population?

MKKS p.Val565= (c.1695T>C) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

How is Bardet-Biedl syndrome inherited?

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

MKKS p.Val565=

c.1695T>C · rs554395344 · VCV1105656

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

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 2.6	GERP 0.35, phastCons 1
Overall
CADD	7.964	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0107% African / African-American · 8/74,952 alleles

Filtering AF 0.00528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.000682% 11/1,612,142 alleles · ultra-rare exomes 7/1,459,832 · genomes 4/152,310 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0107%	9,369
Remaining individualsnot grpmax-eligible	0.0016%	62,434
South Asian	0.0011%	90,716
European (non-Finnish)	8.48e-05%	1,179,071

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.Val565=
Coding: c.1695T>C
MANE Select: NM_170784
dbSNP: rs554395344
Type: single nucleotide variant
Location: chr20:10405265 (GRCh38)
Gene constraint: LOEUF 1.112 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 89.05
Residue 565: 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 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 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-val565 (accessed [today's date]).

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