Is NBAS p.Arg484Cys (c.1450C>T) pathogenic?

NBAS p.Arg484Cys (c.1450C>T) is classified Conflicting classifications of pathogenicity in NBAS (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-24). AlphaMissense: likely benign (0.1841); Ultra-rare (popmax 0.036%, afr); Associated with Inborn genetic diseases.

What condition is associated with NBAS p.Arg484Cys (c.1450C>T)?

NBAS p.Arg484Cys (c.1450C>T) is associated with Inborn genetic diseases (ClinVar).

How common is NBAS p.Arg484Cys (c.1450C>T) in the general population?

NBAS p.Arg484Cys (c.1450C>T) is ultra-rare (popmax 0.036%, afr) (gnomAD).

What do computational predictors say about NBAS p.Arg484Cys (c.1450C>T)?

AlphaMissense predicts likely benign (score 0.1841) — an in-silico prediction, not a clinical call.

NBAS p.Arg484Cys

c.1450C>T · rs145177445 · VCV1424532

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1841 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.036%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1841	likely benign
REVEL	0.288	benign-leaning
SaProt	LLR -9.36	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 1.9, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 394 kb · p 0.09 · regional, not allelic
Overall
CADD	31.0	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 0.036% African / African-American · 27/74,994 alleles

Filtering AF 0.0254% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0219%

Overall 0.00384% 62/1,614,036 alleles · ultra-rare exomes 41/1,461,862 · genomes 21/152,174 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.036%	2,778
Admixed American	0.005%	20,003
Remaining individualsnot grpmax-eligible	0.0048%	20,836
East Asian	0.00223%	44,866
European (non-Finnish)	0.0022%	45,384
South Asian	0.0022%	45,534

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.Arg484Cys
Coding: c.1450C>T
MANE Select: NM_015909
dbSNP: rs145177445
Type: single nucleotide variant
Location: chr2:15474216 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.42
Residue 484: a UniProt-annotated variant site (in ilfs2; uncertain significance); 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.Arg484His 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-arg484cys (accessed [today's date]).

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