Is NBEA p.Pro504Leu (c.1511C>T) pathogenic?

NBEA p.Pro504Leu (c.1511C>T) is classified Uncertain significance in NBEA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-20). AlphaMissense: likely pathogenic (0.9887); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with NBEA p.Pro504Leu (c.1511C>T)?

NBEA p.Pro504Leu (c.1511C>T) is associated with Inborn genetic diseases (ClinVar).

How common is NBEA p.Pro504Leu (c.1511C>T) in the general population?

NBEA p.Pro504Leu (c.1511C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NBEA p.Pro504Leu (c.1511C>T)?

AlphaMissense predicts likely pathogenic (score 0.9887) — an in-silico prediction, not a clinical call.

NBEA p.Pro504Leu

c.1511C>T · VCV3402929

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9887 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9887	likely pathogenic
REVEL	0.609	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 86 kb · p 2.9e-12 · regional, not allelic
Overall
CADD	27.4	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

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: NBEA
Protein: p.Pro504Leu
Coding: c.1511C>T
MANE Select: NM_001385012
Type: single nucleotide variant
Location: chr13:35070792 (GRCh38)
Gene constraint: LOEUF 0.137 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 504: a UniProt-annotated variant site (in nedege)

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-pro504leu (accessed [today's date]).

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