Is NBEA p.Ala755Pro (c.2263G>C) pathogenic?

NBEA p.Ala755Pro (c.2263G>C) is classified Uncertain significance in NBEA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-11). AlphaMissense: likely pathogenic (0.911); No allele count reported in gnomAD v4.1 (AN 1,518,648).

How common is NBEA p.Ala755Pro (c.2263G>C) in the general population?

NBEA p.Ala755Pro (c.2263G>C) is no allele count reported in gnomAD v4.1 (AN 1,518,648) (gnomAD).

What do computational predictors say about NBEA p.Ala755Pro (c.2263G>C)?

AlphaMissense predicts likely pathogenic (score 0.911) — an in-silico prediction, not a clinical call.

NBEA p.Ala755Pro

c.2263G>C · VCV3372482

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.911 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,518,648)

Computational evidence

Protein change
AlphaMissense	0.911	likely pathogenic
REVEL	0.584	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 86 kb · p 2.9e-12 · regional, not allelic
Overall
CADD	29.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,518,648). 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: NBEA
Protein: p.Ala755Pro
Coding: c.2263G>C
MANE Select: NM_001385012
Type: single nucleotide variant
Location: chr13:35123501 (GRCh38)
Gene constraint: LOEUF 0.137 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 755: a UniProt-annotated variant site (in nedege)

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

Similar variants

NBEA p.Arg1299Ter Pathogenic/Likely pathogenic ★★ same type
NBEA p.Arg145Ter Pathogenic/Likely pathogenic ★★ same type
NBEA p.Arg2213Ter Pathogenic/Likely pathogenic ★★ same type
NBEA p.Arg2866Ter Pathogenic ★★ same type
NBEA p.Arg696Ter Pathogenic/Likely pathogenic ★★ same type
NBEA p.Asp319Tyr Likely pathogenic ★★ same type
NBEA c.4242+5G>A Uncertain significance ★★ same type
NBEA p.Ala603Val Uncertain significance ★★ same type

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-ala755pro (accessed [today's date]).

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