SASS6

Chr 1AR

SAS-6 centriolar assembly protein

Also known as: MCPH14, SAS-6, SAS6

NCBI Gene: 163786 ENSG00000156876 UniProt: Q6UVJ0 OMIM: 609321

The protein forms the central hub and spokes of the cartwheel-shaped centriole structure and is essential for centriole duplication and function within the centrosome. Mutations cause autosomal recessive primary microcephaly 14 through a loss-of-function mechanism that disrupts normal centriole formation and cell division.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

The protein encoded by this gene is a central component of centrioles and is necessary for their duplication and function. Centrioles adopt a cartwheel-shaped structure, with the encoded protein forming the hub and spokes inside a microtubule cylinder. Defects in this gene are a cause of autosomal recessive primary microcephaly. [provided by RefSeq, Oct 2016]

OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 0.681 OMIM phenotype

Clinical Summary— SASS6

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

7 unique Pathogenic / Likely Pathogenic· 77 VUS of 157 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.68LOEUF

pLI 0.000

Z-score 3.15

OE 0.46 (0.32–0.68)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.01Z-score

OE missense 0.84 (0.76–0.93)

261 obs / 311.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.46 (0.32–0.68)

0≤0.351.4

Missense OE?0.84 (0.76–0.93)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 18 / 39.3Missense obs/exp: 261 / 311.0Syn Z: -0.24

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

moderateSASS6-related severe microcephaly with brain abnormalitiesOTHERAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.7131th %ile

GOF

0.5170th %ile

LOF

0.3551th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

157 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

Likely Pathogenic4

VUS77

Likely Benign26

Benign39

Conflicting2

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	1	0	0	3
Likely Pathogenic	3	0	1	0	4
VUS	1	76	0	0	77
Likely Benign	0	12	6	8	26
Benign	0	3	31	5	39
Conflicting	—				2
Total	6	92	38	13	151

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

9 pathogenic / likely-pathogenic (of 14) ClinVar copy-number / structural variants overlap SASS6 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →