Is MANBA p.Ala684Val (c.2051C>T) pathogenic?

MANBA p.Ala684Val (c.2051C>T) is classified Uncertain significance in MANBA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-28). AlphaMissense: likely benign (0.18); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with MANBA p.Ala684Val (c.2051C>T)?

MANBA p.Ala684Val (c.2051C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MANBA p.Ala684Val (c.2051C>T) in the general population?

MANBA p.Ala684Val (c.2051C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MANBA p.Ala684Val (c.2051C>T)?

AlphaMissense predicts likely benign (score 0.18) — an in-silico prediction, not a clinical call.

MANBA p.Ala684Val

c.2051C>T · VCV4102872

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.18 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.18	likely benign
REVEL	0.557	indeterminate
SaProt	LLR -10.30	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 129 kb · p 0.31 · regional, not allelic
Overall
CADD	26.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MANBA
Protein: p.Ala684Val
Coding: c.2051C>T
MANE Select: NM_005908
Type: single nucleotide variant
Location: chr4:102635971 (GRCh38)
Gene constraint: LOEUF 0.826 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.05
Residue 684: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MANBA p.Ala147Val Uncertain significance ★★ ⚠ same condition
MANBA p.Arg273Lys Uncertain significance ★★ ⚠ same condition
MANBA p.Asp713Val Uncertain significance ★★ ⚠ same condition
MANBA p.Asp813Val Uncertain significance ★★ ⚠ same condition
MANBA p.Cys761Ser Uncertain significance ★★ ⚠ same condition
MANBA p.Glu234Lys Uncertain significance ★★ ⚠ same condition
MANBA p.Glu848Lys Uncertain significance ★★ ⚠ same condition
MANBA p.Gly102Arg Uncertain significance ★★ ⚠ 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-ala684val (accessed [today's date]).

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