Is MANBA p.Lys85Arg (c.254A>G) pathogenic?

MANBA p.Lys85Arg (c.254A>G) is classified Uncertain significance in MANBA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-16). AlphaMissense: likely benign (0.0727); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with MANBA p.Lys85Arg (c.254A>G)?

MANBA p.Lys85Arg (c.254A>G) is associated with Inborn genetic diseases (ClinVar).

How common is MANBA p.Lys85Arg (c.254A>G) in the general population?

MANBA p.Lys85Arg (c.254A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MANBA p.Lys85Arg (c.254A>G)?

AlphaMissense predicts likely benign (score 0.0727) — an in-silico prediction, not a clinical call.

MANBA p.Lys85Arg

c.254A>G · VCV4102873

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0727 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,536,956)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0727	likely benign
REVEL	0.017	moderately benign-leaning
SaProt	LLR -7.00	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.34	GERP -1, phastCons 0.075
Regional constraint	o/e 0.97	unconstrained · MANE · 129 kb · p 0.31 · regional, not allelic
Overall
CADD	12.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,536,956). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MANBA
Protein: p.Lys85Arg
Coding: c.254A>G
MANE Select: NM_005908
Type: single nucleotide variant
Location: chr4:102726607 (GRCh38)
Gene constraint: LOEUF 0.826 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.05

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-lys85arg (accessed [today's date]).

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