Is MANBA p.Ala802Val (c.2405C>T) pathogenic?

MANBA p.Ala802Val (c.2405C>T) is classified Uncertain significance in MANBA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-04-10). AlphaMissense: likely benign (0.165); Very rare (popmax 0.00668%, eas); Associated with beta-mannosidosis.

What condition is associated with MANBA p.Ala802Val (c.2405C>T)?

MANBA p.Ala802Val (c.2405C>T) is associated with beta-mannosidosis (ClinVar).

How common is MANBA p.Ala802Val (c.2405C>T) in the general population?

MANBA p.Ala802Val (c.2405C>T) is very rare (popmax 0.00668%, eas) (gnomAD).

How is Beta-mannosidosis inherited?

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

What do computational predictors say about MANBA p.Ala802Val (c.2405C>T)?

AlphaMissense predicts likely benign (score 0.165) — an in-silico prediction, not a clinical call.

MANBA p.Ala802Val

c.2405C>T · rs778265593 · VCV2142284

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.165 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

beta-mannosidosis

Computational evidence

Protein change
AlphaMissense	0.165	likely benign
REVEL	0.169	moderately benign-leaning
SaProt	LLR -10.44	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	Δ0.75	donor gain · deltas
Pangolin	Δ0.30	gain · loss 0.07 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 9.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 129 kb · p 0.31 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% East Asian · 3/44,900 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.00105% 17/1,613,558 alleles · very rare exomes 16/1,461,338 · genomes 1/152,220 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,967
Admixed American	0.00333%	30,005
South Asian	0.0022%	45,530
Finnishnot grpmax-eligible	0.00156%	64,044
European (non-Finnish)	0.000763%	131,115

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: MANBA
Protein: p.Ala802Val
Coding: c.2405C>T
MANE Select: NM_005908
dbSNP: rs778265593
Type: single nucleotide variant
Location: chr4:102634798 (GRCh38)
Gene constraint: LOEUF 0.826 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.05
Residue 802: a UniProt-annotated variant site (in mansb; complete loss of enzyme activity)

Full MANBA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

beta-mannosidosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Beta-mannosidosis (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

MANBA p.Ala802= Likely benign ★★ same residue
MANBA c.1112+1G>T Likely pathogenic ★★ same condition
MANBA c.1231-1G>A Likely pathogenic ★★ same condition
MANBA c.1704+1G>T Likely pathogenic ★★ same condition
MANBA c.2158-2A>G Pathogenic ★★ same condition
MANBA c.273-1G>A Likely pathogenic ★★ same condition
MANBA c.378+1G>A Likely pathogenic ★★ same condition
MANBA c.549+1G>A 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/manba-p-ala802val (accessed [today's date]).

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