Is NBAS p.Ile994Val (c.2980A>G) pathogenic?

NBAS p.Ile994Val (c.2980A>G) is classified Likely benign in NBAS (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-05). AlphaMissense: likely benign (0.0574); Ultra-rare (popmax 0.0567%, amr); Associated with Inborn genetic diseases.

What condition is associated with NBAS p.Ile994Val (c.2980A>G)?

NBAS p.Ile994Val (c.2980A>G) is associated with Inborn genetic diseases (ClinVar).

How common is NBAS p.Ile994Val (c.2980A>G) in the general population?

NBAS p.Ile994Val (c.2980A>G) is ultra-rare (popmax 0.0567%, amr) (gnomAD).

What do computational predictors say about NBAS p.Ile994Val (c.2980A>G)?

AlphaMissense predicts likely benign (score 0.0574) — an in-silico prediction, not a clinical call.

NBAS p.Ile994Val

c.2980A>G · rs538790933 · VCV1484411

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0574 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0567%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0574	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -7.50	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 -6.1	GERP -3.5
Regional constraint	o/e 1.03	unconstrained · MANE · 394 kb · p 0.09 · regional, not allelic
Overall
CADD	0.071	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 0.0567% Admixed American · 34/59,988 alleles

Filtering AF 0.0416% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0365%

Overall 0.00682% 110/1,613,500 alleles · ultra-rare exomes 101/1,461,314 · genomes 9/152,186 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0567%	1,764
Remaining individualsnot grpmax-eligible	0.00961%	10,411
African / African-American	0.00534%	18,728
European (non-Finnish)	0.005%	19,994
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,584
South Asian	0.00329%	30,358
Finnishnot grpmax-eligible	0.00312%	32,016
East Asian	0.00223%	44,804

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.Ile994Val
Coding: c.2980A>G
MANE Select: NM_015909
dbSNP: rs538790933
Type: single nucleotide variant
Location: chr2:15402259 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.42
Residue 994: 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

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NBAS p.Ala1941Gly Uncertain significance ★★ ⚠ same condition
NBAS p.Ala195Thr Uncertain significance ★★ ⚠ same condition
NBAS p.Ala2005Thr Uncertain significance ★★ ⚠ same condition
NBAS p.Ala2341Val Uncertain significance ★★ ⚠ same condition
NBAS p.Ala48Ser 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-ile994val (accessed [today's date]).

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