SASS6

Chr 1AR

SAS-6 centriolar assembly protein

Also known as: MCPH14, SAS-6, SAS6

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.

Summary from RefSeq, OMIM, UniProt, Mechanism
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Primary Disease Associations & Inheritance

Microcephaly 14, primary, autosomal recessiveMIM #616402
AR
0
Active trials
4
Pubs (1 yr)
12
P/LP submissions
9%
P/LP missense
0.68
LOEUF
DN
Mechanism· predicted
Clinical SummarySASS6
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
11 unique Pathogenic / Likely Pathogenic· 4 VUS of 69 total submissions
Some data sources returned errors (1)

ensembl: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.68LOEUF
pLI 0.000
Z-score 3.15
OE 0.46 (0.320.68)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.01Z-score
OE missense 0.84 (0.760.93)
261 obs / 311.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.46 (0.320.68)
00.351.4
Missense OE0.84 (0.760.93)
00.61.4
Synonymous OE1.03
01.21.6
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

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

DN
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

69 submitted variants in ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic2
VUS4
Likely Benign13
Benign40
Conflicting1
9
Pathogenic
2
Likely Pathogenic
4
VUS
13
Likely Benign
40
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
1
6
0
9
Likely Pathogenic
1
0
1
0
2
VUS
0
3
1
0
4
Likely Benign
0
4
4
5
13
Benign
0
4
31
5
40
Conflicting
1
Total312431069

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

View in ClinVar →

Protein Context — Lollipop Plot

SASS6 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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