Is NBAS p.Asp987Ala (c.2960A>C) pathogenic?

NBAS p.Asp987Ala (c.2960A>C) is classified Conflicting classifications of pathogenicity in NBAS (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.2552); Ultra-rare (popmax 0.0637%, sas); Associated with Inborn genetic diseases.

What condition is associated with NBAS p.Asp987Ala (c.2960A>C)?

NBAS p.Asp987Ala (c.2960A>C) is associated with Inborn genetic diseases (ClinVar).

How common is NBAS p.Asp987Ala (c.2960A>C) in the general population?

NBAS p.Asp987Ala (c.2960A>C) is ultra-rare (popmax 0.0637%, sas) (gnomAD).

What do computational predictors say about NBAS p.Asp987Ala (c.2960A>C)?

AlphaMissense predicts likely benign (score 0.2552) — an in-silico prediction, not a clinical call.

NBAS p.Asp987Ala

c.2960A>C · rs772389513 · VCV1418956

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2552 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0637%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2552	likely benign
REVEL	0.29	benign-leaning
SaProt	LLR -10.55	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 0.65, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 394 kb · p 0.09 · regional, not allelic
Overall
CADD	25.5	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

Grpmax group 0.0637% South Asian · 58/91,072 alleles

Filtering AF 0.0505% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0458%

Overall 0.00372% 60/1,613,490 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0637%	1,570
Remaining individualsnot grpmax-eligible	0.0032%	31,232

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: NBAS
Protein: p.Asp987Ala
Coding: c.2960A>C
MANE Select: NM_015909
dbSNP: rs772389513
Type: single nucleotide variant
Location: chr2:15402279 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.42
Residue 987: a UniProt-annotated variant site (in ilfs2; uncertain significance); a UniProt-annotated variant site (found in a patient with a multisystem disease involving liver, eye, immune system, connective tissue and bone; uncertain significance); a UniProt-annotated variant site (found in a patient with a multisystem disease involving liver, eye, immune system, connective tissue and bone; uncertain significance; reduced protein expression levels in fibroblasts); the 'interaction with use1' region

Full NBAS 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

NBAS p.Asp987Asn Uncertain significance ★ ⚠ same residue
NBAS p.Ala1568Val Uncertain significance ★★ ⚠ same condition
NBAS p.Ala1645Val Uncertain significance ★★ ⚠ same condition
NBAS p.Ala1795Val Uncertain significance ★★ ⚠ same condition
NBAS p.Ala1941Gly Uncertain significance ★★ ⚠ same condition
NBAS p.Ala195Thr Uncertain significance ★★ ⚠ same condition
NBAS p.Ala2005Thr Uncertain significance ★★ ⚠ same condition
NBAS p.Ala2341Val 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/nbas-p-asp987ala (accessed [today's date]).

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