Is NBEA p.Arg149Gln (c.446G>A) pathogenic?

NBEA p.Arg149Gln (c.446G>A) is classified Uncertain significance in NBEA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-16). AlphaMissense: ambiguous (0.4907); Very rare (popmax 0.00401%, afr); Associated with Inborn genetic diseases.

What condition is associated with NBEA p.Arg149Gln (c.446G>A)?

NBEA p.Arg149Gln (c.446G>A) is associated with Inborn genetic diseases (ClinVar).

How common is NBEA p.Arg149Gln (c.446G>A) in the general population?

NBEA p.Arg149Gln (c.446G>A) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about NBEA p.Arg149Gln (c.446G>A)?

AlphaMissense predicts ambiguous (score 0.4907) — an in-silico prediction, not a clinical call.

NBEA p.Arg149Gln

c.446G>A · rs983917648 · VCV3178292

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4907 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4907	ambiguous
REVEL	0.359	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 107 kb · p 5.9e-10 · regional, not allelic
Overall
CADD	28.0	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 0.00401% African / African-American · 3/74,840 alleles

Filtering AF 0.00267% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00236%

Overall 0.00291% 47/1,612,938 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,947
European (non-Finnish)	0.00356%	28,082
Remaining individualsnot grpmax-eligible	0.0032%	31,210

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: NBEA
Protein: p.Arg149Gln
Coding: c.446G>A
MANE Select: NM_001385012
dbSNP: rs983917648
Type: single nucleotide variant
Location: chr13:35041084 (GRCh38)
Gene constraint: LOEUF 0.137 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)

Full NBEA 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

NBEA p.Arg1299Ter Pathogenic/Likely pathogenic ★★ same condition
NBEA p.Arg1325Gln Uncertain significance ★★ same condition
NBEA p.Arg2277Gln Uncertain significance ★★ same condition
NBEA p.Arg2291Gly Uncertain significance ★★ ⚠ same condition
NBEA p.Asp701Glu Uncertain significance ★★ ⚠ same condition
NBEA p.Gln2141Arg Uncertain significance ★★ ⚠ same condition
NBEA p.Glu971Asp Uncertain significance ★★ ⚠ same condition
NBEA p.Gly39Asp 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/nbea-p-arg149gln (accessed [today's date]).

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