Is NBEA p.Ser2808Pro (c.8422T>C) pathogenic?

NBEA p.Ser2808Pro (c.8422T>C) is classified Likely pathogenic in NBEA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-16). AlphaMissense: likely pathogenic (0.9904); Absent from gnomAD v4.1; Associated with neurodevelopmental disorder with or without early-onset generalized epilepsy.

What condition is associated with NBEA p.Ser2808Pro (c.8422T>C)?

NBEA p.Ser2808Pro (c.8422T>C) is associated with neurodevelopmental disorder with or without early-onset generalized epilepsy (ClinVar).

How common is NBEA p.Ser2808Pro (c.8422T>C) in the general population?

NBEA p.Ser2808Pro (c.8422T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NBEA p.Ser2808Pro (c.8422T>C)?

AlphaMissense predicts likely pathogenic (score 0.9904) — an in-silico prediction, not a clinical call.

NBEA p.Ser2808Pro

c.8422T>C · VCV4071976

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9904 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Conditions

neurodevelopmental disorder with or without early-onset generalized epilepsy

Computational evidence

Protein change
AlphaMissense	0.9904	likely pathogenic ✓ concordant with ClinVar
REVEL	0.257	benign-leaning
⇒ AlphaMissense calls this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP -1.1, phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 16 kb · p 3.2e-15 · regional, not allelic
Overall
CADD	28.2	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S2787P vs ClinVar S2808P) — verify the residue.

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.Ser2808Pro
Coding: c.8422T>C
MANE Select: NM_001385012
Type: single nucleotide variant
Location: chr13:35665144 (GRCh38)
Gene constraint: LOEUF 0.137 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2808: a UniProt-annotated variant site (in nedege); a UniProt-annotated variant site (in nedege; uncertain significance)

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.Ser2808= Likely benign ★ 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-ser2808pro (accessed [today's date]).

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