Is NBAS p.Leu917Ser (c.2750T>C) pathogenic?

NBAS p.Leu917Ser (c.2750T>C) is classified Conflicting classifications of pathogenicity in NBAS (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-28). AlphaMissense: ambiguous (0.4296); Rare (popmax 0.409%, afr); Associated with Inborn genetic diseases.

What condition is associated with NBAS p.Leu917Ser (c.2750T>C)?

NBAS p.Leu917Ser (c.2750T>C) is associated with Inborn genetic diseases (ClinVar).

How common is NBAS p.Leu917Ser (c.2750T>C) in the general population?

NBAS p.Leu917Ser (c.2750T>C) is rare (popmax 0.409%, afr) (gnomAD).

What do computational predictors say about NBAS p.Leu917Ser (c.2750T>C)?

AlphaMissense predicts ambiguous (score 0.4296) — an in-silico prediction, not a clinical call.

NBAS p.Leu917Ser

c.2750T>C · rs140950764 · VCV721145

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

ambiguous

0.4296 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.409%, afr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4296	ambiguous
REVEL	0.713	pathogenic-leaning
SaProt	LLR -10.54	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 394 kb · p 0.09 · regional, not allelic
Overall
CADD	26.5	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 0.409% African / African-American · 307/74,978 alleles

Filtering AF 0.372% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.357%

Overall 0.0209% 337/1,612,656 alleles · rare exomes 155/1,460,342 · genomes 182/152,314 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.409%	244
Middle Eastern	0.066%	1,514
Remaining individualsnot grpmax-eligible	0.0304%	3,287
Admixed American	0.00833%	12,003
South Asian	0.0011%	91,028
European (non-Finnish)	8.48e-05%	1,178,806

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.Leu917Ser
Coding: c.2750T>C
MANE Select: NM_015909
dbSNP: rs140950764
Type: single nucleotide variant
Location: chr2:15417540 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.42
Residue 917: 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); a UniProt-annotated variant site (found in a patient with a multisystem disease involving liver, eye, immune system, connective tissue and bone; uncertain significance; reduced protein expression levels in fibroblasts); 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.Leu917Ile Uncertain significance ★ ⚠ same residue
NBAS p.Leu917= 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

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-leu917ser (accessed [today's date]).

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