Is NBAS p.Ala1941Val (c.5822C>T) pathogenic?

NBAS p.Ala1941Val (c.5822C>T) is classified Uncertain significance in NBAS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-19). AlphaMissense: likely benign (0.0628); Very rare (popmax 0.00892%, eas); Associated with Inborn genetic diseases.

What condition is associated with NBAS p.Ala1941Val (c.5822C>T)?

NBAS p.Ala1941Val (c.5822C>T) is associated with Inborn genetic diseases (ClinVar).

How common is NBAS p.Ala1941Val (c.5822C>T) in the general population?

NBAS p.Ala1941Val (c.5822C>T) is very rare (popmax 0.00892%, eas) (gnomAD).

What do computational predictors say about NBAS p.Ala1941Val (c.5822C>T)?

AlphaMissense predicts likely benign (score 0.0628) — an in-silico prediction, not a clinical call.

NBAS p.Ala1941Val

c.5822C>T · rs370974818 · VCV2599130

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0628 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00892%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0628	likely benign
REVEL	0.068	moderately benign-leaning
SaProt	LLR -6.62	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 -0.019	GERP -5.2
Regional constraint	o/e 1.03	unconstrained · MANE · 394 kb · p 0.09 · regional, not allelic
Overall
CADD	0.026	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00892% East Asian · 4/44,868 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00031% 5/1,613,718 alleles · very rare exomes 4/1,461,654 · genomes 1/152,064 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00892%	11,217
Remaining individualsnot grpmax-eligible	0.0016%	62,470

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.Ala1941Val
Coding: c.5822C>T
MANE Select: NM_015909
dbSNP: rs370974818
Type: single nucleotide variant
Location: chr2:15238589 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.42
Residue 1941: 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); 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 collagen secretion; diffuse collagen bundles; reduced protein expression in fibroblasts); the 'interaction with zw10 and rint1' 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.Ala1941Gly Uncertain significance ★★ ⚠ 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.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-ala1941val (accessed [today's date]).

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