MANEAL

Chr 1

mannosidase endo-alpha like

NCBI Gene: 149175 ENSG00000185090 UniProt: Q5VSG8 OMIM: 620919

The protein is predicted to function as an alpha-mannosidase in the Golgi membrane, involved in carbohydrate processing. Mutations cause autosomal recessive intellectual disability with seizures and spasticity. The gene shows tolerance to loss-of-function variants, consistent with a recessive inheritance pattern.

OMIM ResearchSummary from RefSeq

Predicted to enable alpha-mannosidase activity. Predicted to be located in Golgi membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 0.85

Clinical Summary— MANEAL

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Population Constraint (gnomAD)

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

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 60 VUS of 66 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.85LOEUF

pLI 0.005

Z-score 1.96

OE 0.43 (0.24–0.85)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.38Z-score

OE missense 0.93 (0.83–1.04)

215 obs / 231.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.43 (0.24–0.85)

0≤0.351.4

Missense OE?0.93 (0.83–1.04)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 6 / 13.9Missense obs/exp: 215 / 231.1Syn Z: 0.53

ClinVar Variant Classifications

66 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic1

VUS60

Likely Benign4

Likely Pathogenic

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Total
Pathogenic	0	0	0
Likely Pathogenic	1	0	1
VUS	0	60	60
Likely Benign	0	4	4
Benign	0	0	0
Total	1	64	65

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

View in ClinVar →

5 pathogenic / likely-pathogenic (of 11) ClinVar copy-number / structural variants overlap MANEAL — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →