Is NBAS p.Pro764Ser (c.2290C>T) pathogenic?

NBAS p.Pro764Ser (c.2290C>T) is classified Uncertain significance in NBAS (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-12-30). AlphaMissense: likely pathogenic (0.6037); Ultra-rare (popmax 0.0329%, mid); Associated with Inborn genetic diseases.

What condition is associated with NBAS p.Pro764Ser (c.2290C>T)?

NBAS p.Pro764Ser (c.2290C>T) is associated with Inborn genetic diseases, neurodevelopmental disorder (ClinVar).

How common is NBAS p.Pro764Ser (c.2290C>T) in the general population?

NBAS p.Pro764Ser (c.2290C>T) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about NBAS p.Pro764Ser (c.2290C>T)?

AlphaMissense predicts likely pathogenic (score 0.6037) — an in-silico prediction, not a clinical call.

NBAS p.Pro764Ser

c.2290C>T · rs200532922 · VCV1436957

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.6037 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6037	likely pathogenic
REVEL	0.638	indeterminate
SaProt	LLR -4.96	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 394 kb · p 0.09 · regional, not allelic
Overall
CADD	28.6	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 0.0329% Middle Eastern · 2/6,080 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00241%

Overall 0.00347% 56/1,613,756 alleles · ultra-rare exomes 53/1,461,644 · genomes 3/152,112 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0709%	1,410
Middle Easterngrpmax	0.0329%	3,040
Remaining individualsnot grpmax-eligible	0.0096%	10,413
Admixed American	0.00833%	11,998
European (non-Finnish)	0.00186%	53,630

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro764Ser
Coding: c.2290C>T
MANE Select: NM_015909
dbSNP: rs200532922
Type: single nucleotide variant
Location: chr2:15461250 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.42
Residue 764: 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

Also linked: neurodevelopmental disorder

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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-pro764ser (accessed [today's date]).

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