Is NBEA p.Asp1663Gly (c.4988A>G) pathogenic?

NBEA p.Asp1663Gly (c.4988A>G) is classified Likely benign in NBEA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-02). AlphaMissense: likely benign (0.1419); Ultra-rare (popmax 0.0991%, mid).

How common is NBEA p.Asp1663Gly (c.4988A>G) in the general population?

NBEA p.Asp1663Gly (c.4988A>G) is ultra-rare (popmax 0.0991%, mid) (gnomAD).

What do computational predictors say about NBEA p.Asp1663Gly (c.4988A>G)?

AlphaMissense predicts likely benign (score 0.1419) — an in-silico prediction, not a clinical call.

NBEA p.Asp1663Gly

c.4988A>G · VCV4919791

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1419 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0991%, mid)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.1419	likely benign
REVEL	0.097	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.1	GERP 2.8, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 26 kb · p 0.17 · regional, not allelic
Overall
CADD	23.2	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

Grpmax group 0.0991% Middle Eastern · 6/6,054 alleles

Filtering AF 0.0432% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0325%

Overall 0.0139% 225/1,613,248 alleles · ultra-rare exomes 192/1,460,952 · genomes 33/152,296 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.284%	352
Middle Easterngrpmax	0.0991%	1,009
Admixed American	0.0517%	1,933
Remaining individualsnot grpmax-eligible	0.0208%	4,804
European (non-Finnish)	0.00704%	14,212
African / African-American	0.00667%	15,002
East Asian	0.00447%	22,393
South Asian	0.0011%	90,946

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: NBEA
Protein: p.Asp1663Gly
Coding: c.4988A>G
MANE Select: NM_001385012
Type: single nucleotide variant
Location: chr13:35195924 (GRCh38)
Gene constraint: LOEUF 0.137 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1663: the 'disordered' region; 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-asp1663gly (accessed [today's date]).

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