Is NBEA p.Asp319Tyr (c.955G>T) pathogenic?

NBEA p.Asp319Tyr (c.955G>T) is classified Likely pathogenic in NBEA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-09-27). AlphaMissense: likely pathogenic (0.9697); Absent from gnomAD v4.1; Associated with NBEA-related complex neurodevelopmental disorder.

What condition is associated with NBEA p.Asp319Tyr (c.955G>T)?

NBEA p.Asp319Tyr (c.955G>T) is associated with NBEA-related complex neurodevelopmental disorder (ClinVar).

How common is NBEA p.Asp319Tyr (c.955G>T) in the general population?

NBEA p.Asp319Tyr (c.955G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NBEA p.Asp319Tyr (c.955G>T)?

AlphaMissense predicts likely pathogenic (score 0.9697) — an in-silico prediction, not a clinical call.

NBEA p.Asp319Tyr

c.955G>T · rs2152563427 · VCV1328525

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9697 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

NBEA-related complex neurodevelopmental disorder

Computational evidence

Protein change
AlphaMissense	0.9697	likely pathogenic ✓ concordant with ClinVar
REVEL	0.71	pathogenic-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.32	constrained · MANE · 20 kb · p 5.7e-26 · regional, not allelic
Overall
CADD	31.0	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

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.Asp319Tyr
Coding: c.955G>T
MANE Select: NM_001385012
dbSNP: rs2152563427
Type: single nucleotide variant
Location: chr13:35050378 (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

NBEA-related complex neurodevelopmental disorder

Similar variants

NBEA p.Arg145Ter Pathogenic/Likely pathogenic ★★ same condition
NBEA p.Arg696Ter Pathogenic/Likely pathogenic ★★ same condition
NBEA p.Glu1995Lys Uncertain significance ★★ same condition
NBEA p.Gly41Ala Uncertain significance ★★ ⚠ same condition
NBEA c.2651+1G>A Likely pathogenic ★ same condition
NBEA c.2845-1G>A Likely pathogenic ★ same condition
NBEA p.Arg1302Ter Likely pathogenic ★ same condition
NBEA p.Gly1967Arg Likely pathogenic ★ 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-asp319tyr (accessed [today's date]).

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