Is NBAS p.Ser180Arg (c.540C>G) pathogenic?

NBAS p.Ser180Arg (c.540C>G) is classified Conflicting classifications of pathogenicity in NBAS (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-18). AlphaMissense: likely pathogenic (0.788); Ultra-rare (popmax 0.033%, mid); Associated with Inborn genetic diseases.

What condition is associated with NBAS p.Ser180Arg (c.540C>G)?

NBAS p.Ser180Arg (c.540C>G) is associated with Inborn genetic diseases (ClinVar).

How common is NBAS p.Ser180Arg (c.540C>G) in the general population?

NBAS p.Ser180Arg (c.540C>G) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about NBAS p.Ser180Arg (c.540C>G)?

AlphaMissense predicts likely pathogenic (score 0.788) — an in-silico prediction, not a clinical call.

NBAS p.Ser180Arg

c.540C>G · rs202027230 · VCV1379399

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.788 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.788	likely pathogenic
REVEL	0.251	benign-leaning
SaProt	LLR -7.89	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.24	loss · gain 0.05 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 5.8	GERP 0.94, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 394 kb · p 0.09 · regional, not allelic
Overall
CADD	24.2	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 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.00503% 81/1,611,414 alleles · ultra-rare exomes 74/1,459,754 · genomes 7/151,660 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.139%	722
Middle Easterngrpmax	0.033%	3,031
Remaining individualsnot grpmax-eligible	0.0128%	7,810
Admixed American	0.01%	9,993
South Asian	0.0022%	45,519
European (non-Finnish)	0.00187%	53,605

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: NBAS
Protein: p.Ser180Arg
Coding: c.540C>G
MANE Select: NM_015909
dbSNP: rs202027230
Type: single nucleotide variant
Location: chr2:15536525 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.42
Residue 180: 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.Ser180= 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
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-ser180arg (accessed [today's date]).

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