Is NBAS p.Arg405Ter (c.1213C>T) pathogenic?

NBAS p.Arg405Ter (c.1213C>T) is classified Pathogenic in NBAS (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-04-30). Very rare (popmax 0.00401%, afr); Associated with inherited retinal dystrophy.

How common is NBAS p.Arg405Ter (c.1213C>T) in the general population?

NBAS p.Arg405Ter (c.1213C>T) is very rare (popmax 0.00401%, afr) (gnomAD).

NBAS p.Arg405Ter

Q: What condition is associated with NBAS p.Arg405Ter (c.1213C>T)?

NBAS p.Arg405Ter (c.1213C>T) is associated with inherited retinal dystrophy, acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins, infantile liver failure syndrome 2 (ClinVar).

c.1213C>T · rs376113678 · VCV1335898

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 14 of 52
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2, phastCons 1
Overall
CADD	43.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00401% African / African-American · 3/74,898 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000744% 12/1,613,904 alleles · very rare exomes 11/1,461,784 · genomes 1/152,120 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,966
Admixed American	0.00167%	60,002
European (non-Finnish)	0.000678%	147,495

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.Arg405Ter
Coding: c.1213C>T
MANE Select: NM_015909
dbSNP: rs376113678
Type: single nucleotide variant
Location: chr2:15475815 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.42
Residue 405: 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

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins infantile liver failure syndrome 2

Similar variants

NBAS p.Arg405Gly Uncertain significance ★★ ⚠ same residue
NBAS p.Arg405Gln Uncertain significance ★ ⚠ same residue
NBAS p.Arg405Leu Uncertain significance ★ ⚠ same residue
NBAS p.Arg405= Benign ★ same residue
NBAS c.1726-2A>G Likely pathogenic ★★ same condition
NBAS c.173-2A>G Likely pathogenic ★★ same condition
NBAS c.2423+404G>C Likely pathogenic ★★ same condition
NBAS c.4461+2T>C Likely pathogenic ★★ 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-arg405ter (accessed [today's date]).

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