Is NBAS p.Val592Ile (c.1774G>A) pathogenic?

NBAS p.Val592Ile (c.1774G>A) is classified Conflicting classifications of pathogenicity in NBAS (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-09). AlphaMissense: likely benign (0.1373); Ultra-rare (popmax 0.0147%, nfe); Associated with Inborn genetic diseases.

What condition is associated with NBAS p.Val592Ile (c.1774G>A)?

NBAS p.Val592Ile (c.1774G>A) is associated with Inborn genetic diseases (ClinVar).

How common is NBAS p.Val592Ile (c.1774G>A) in the general population?

NBAS p.Val592Ile (c.1774G>A) is ultra-rare (popmax 0.0147%, nfe) (gnomAD).

What do computational predictors say about NBAS p.Val592Ile (c.1774G>A)?

AlphaMissense predicts likely benign (score 0.1373) — an in-silico prediction, not a clinical call.

NBAS p.Val592Ile

c.1774G>A · rs151116990 · VCV1427428

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1373 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1373	likely benign
REVEL	0.151	moderately benign-leaning
SaProt	LLR -6.59	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 7.7	GERP 1.9, 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

Grpmax group 0.0147% European (non-Finnish) · 173/1,179,972 alleles

Filtering AF 0.0128% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0122%

Overall 0.0113% 182/1,614,088 alleles · ultra-rare exomes 170/1,461,764 · genomes 12/152,324 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0147%	6,821
African / African-American	0.00666%	15,010
Remaining individualsnot grpmax-eligible	0.0048%	20,834
Admixed American	0.00167%	60,008

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.Val592Ile
Coding: c.1774G>A
MANE Select: NM_015909
dbSNP: rs151116990
Type: single nucleotide variant
Location: chr2:15468485 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.42
Residue 592: 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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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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-val592ile (accessed [today's date]).

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