Is NBAS p.Asp1859Val (c.5576A>T) pathogenic?

NBAS p.Asp1859Val (c.5576A>T) is classified Uncertain significance in NBAS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-12). AlphaMissense: ambiguous (0.5523); Very rare (popmax 0.00267%, afr); Associated with Inborn genetic diseases.

What condition is associated with NBAS p.Asp1859Val (c.5576A>T)?

NBAS p.Asp1859Val (c.5576A>T) is associated with Inborn genetic diseases (ClinVar).

How common is NBAS p.Asp1859Val (c.5576A>T) in the general population?

NBAS p.Asp1859Val (c.5576A>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about NBAS p.Asp1859Val (c.5576A>T)?

AlphaMissense predicts ambiguous (score 0.5523) — an in-silico prediction, not a clinical call.

NBAS p.Asp1859Val

c.5576A>T · VCV4117100

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5523 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5523	ambiguous
REVEL	0.667	pathogenic-leaning
SaProt	LLR -4.15	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.9	GERP 2.6, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 394 kb · p 0.09 · regional, not allelic
Overall
CADD	26.3	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 0.00267% African / African-American · 2/74,900 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,613,924 alleles · very rare exomes 0/1,461,804 · genomes 2/152,120 · joint denominator

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.Asp1859Val
Coding: c.5576A>T
MANE Select: NM_015909
Type: single nucleotide variant
Location: chr2:15275632 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.42
Residue 1859: 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); 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 collagen secretion; diffuse collagen bundles; reduced protein expression in fibroblasts); the 'interaction with zw10 and rint1' 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.Asp1859Tyr Uncertain significance ★★ same residue
NBAS p.Asp1859Glu Uncertain significance ★ same residue
NBAS p.Asp1859= Likely benign ★ 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

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-asp1859val (accessed [today's date]).

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