Is NBAS p.Arg522Ser (c.1564C>A) pathogenic?

NBAS p.Arg522Ser (c.1564C>A) is classified Uncertain significance in NBAS (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-22). AlphaMissense: likely pathogenic (0.7659); Absent from gnomAD v4.1.

How common is NBAS p.Arg522Ser (c.1564C>A) in the general population?

NBAS p.Arg522Ser (c.1564C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NBAS p.Arg522Ser (c.1564C>A)?

AlphaMissense predicts likely pathogenic (score 0.7659) — an in-silico prediction, not a clinical call.

NBAS p.Arg522Ser

c.1564C>A · rs187987936 · VCV1478517

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7659 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7659	likely pathogenic
REVEL	0.238	benign-leaning
SaProt	LLR -7.66	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 1.1, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 394 kb · p 0.09 · regional, not allelic
Overall
CADD	23.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: NBAS
Protein: p.Arg522Ser
Coding: c.1564C>A
MANE Select: NM_015909
dbSNP: rs187987936
Type: single nucleotide variant
Location: chr2:15474102 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.42
Residue 522: 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.Arg522Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
NBAS p.Arg522His Uncertain significance ★ ⚠ same residue
NBAS p.Arg522Leu Uncertain significance ★ 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

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-arg522ser (accessed [today's date]).

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