Is NBEA p.Pro246Ser (c.736C>T) pathogenic?

NBEA p.Pro246Ser (c.736C>T) is classified Uncertain significance in NBEA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-16). AlphaMissense: likely pathogenic (0.9669); Absent from gnomAD v4.1; Associated with neurodevelopmental disorder with or without early-onset generalized epilepsy.

What condition is associated with NBEA p.Pro246Ser (c.736C>T)?

NBEA p.Pro246Ser (c.736C>T) is associated with neurodevelopmental disorder with or without early-onset generalized epilepsy (ClinVar).

How common is NBEA p.Pro246Ser (c.736C>T) in the general population?

NBEA p.Pro246Ser (c.736C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NBEA p.Pro246Ser (c.736C>T)?

AlphaMissense predicts likely pathogenic (score 0.9669) — an in-silico prediction, not a clinical call.

NBEA p.Pro246Ser

c.736C>T · VCV4531451

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9669 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,607,474)

Conditions

neurodevelopmental disorder with or without early-onset generalized epilepsy

Computational evidence

Protein change
AlphaMissense	0.9669	likely pathogenic
REVEL	0.608	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 107 kb · p 5.9e-10 · regional, not allelic
Overall
CADD	26.6	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

No allele count reported in gnomAD v4.1 (AN 1,607,474). 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.Pro246Ser
Coding: c.736C>T
MANE Select: NM_001385012
Type: single nucleotide variant
Location: chr13:35048575 (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

neurodevelopmental disorder with or without early-onset generalized epilepsy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NBEA p.Pro246Leu Uncertain significance ★ ⚠ same residue
NBEA p.Arg1299Ter Pathogenic/Likely pathogenic ★★ same condition
NBEA p.Arg2866Ter Pathogenic ★★ same condition
NBEA p.Arg696Ter Pathogenic/Likely pathogenic ★★ same condition
NBEA p.Ala603Val Uncertain significance ★★ same condition
NBEA p.Asn1141Asp Uncertain significance ★★ ⚠ same condition
NBEA p.Asn1599Ser Uncertain significance ★★ ⚠ same condition
NBEA p.Asp2789Asn 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-pro246ser (accessed [today's date]).

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