Is NBAS p.Arg508Cys (c.1522C>T) pathogenic?

NBAS p.Arg508Cys (c.1522C>T) is classified Likely benign in NBAS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-28). AlphaMissense: likely benign (0.2746); Ultra-rare (popmax 0.0318%, sas).

How common is NBAS p.Arg508Cys (c.1522C>T) in the general population?

NBAS p.Arg508Cys (c.1522C>T) is ultra-rare (popmax 0.0318%, sas) (gnomAD).

What do computational predictors say about NBAS p.Arg508Cys (c.1522C>T)?

AlphaMissense predicts likely benign (score 0.2746) — an in-silico prediction, not a clinical call.

NBAS p.Arg508Cys

c.1522C>T · rs367964914 · VCV1480683

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2746 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0318%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2746	likely benign
REVEL	0.494	indeterminate
SaProt	LLR -9.50	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.1, 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 0.0318% South Asian · 29/91,086 alleles

Filtering AF 0.0228% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0196%

Overall 0.00335% 54/1,614,000 alleles · ultra-rare exomes 43/1,461,876 · genomes 11/152,124 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0318%	3,141
African / African-American	0.012%	8,322
Admixed American	0.005%	19,997
Remaining individualsnot grpmax-eligible	0.0048%	20,829
East Asian	0.00446%	22,438
European (non-Finnish)	0.000678%	147,504

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.Arg508Cys
Coding: c.1522C>T
MANE Select: NM_015909
dbSNP: rs367964914
Type: single nucleotide variant
Location: chr2:15474144 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.42
Residue 508: 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); the 'interaction with use1' region

Full NBAS gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NBAS p.Arg508His Conflicting classifications of pathogenicity ★ ⚠ same residue
NBAS p.Arg508= Likely benign ★ same residue
NBAS c.1726-2A>G Likely pathogenic ★★ same type
NBAS c.173-2A>G Likely pathogenic ★★ same type
NBAS c.209+2T>G Pathogenic/Likely pathogenic ★★ same type
NBAS c.2423+404G>C Likely pathogenic ★★ same type
NBAS c.335+1G>C Pathogenic/Likely pathogenic ★★ same type
NBAS c.4461+2T>C Likely pathogenic ★★ 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/nbas-p-arg508cys (accessed [today's date]).

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