Is NBAS p.Asp693= (c.2079T>C) pathogenic?

NBAS p.Asp693= (c.2079T>C) is classified Likely benign in NBAS (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-27). Ultra-rare (popmax 0.0202%, nfe).

How common is NBAS p.Asp693= (c.2079T>C) in the general population?

NBAS p.Asp693= (c.2079T>C) is ultra-rare (popmax 0.0202%, nfe) (gnomAD).

NBAS p.Asp693=

c.2079T>C · rs146792030 · VCV1090756

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0202%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP -2.1, phastCons 1
Overall
CADD	7.701	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0202% European (non-Finnish) · 238/1,179,106 alleles

Filtering AF 0.0181% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0172%

Overall 0.0161% 259/1,612,840 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0224%	4,459
European (non-Finnish)grpmax	0.0202%	4,954
African / African-American	0.00668%	14,978
Finnishnot grpmax-eligible	0.00312%	32,011

Remaining individuals 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.Asp693=
Coding: c.2079T>C
MANE Select: NM_015909
dbSNP: rs146792030
Type: single nucleotide variant
Location: chr2:15467347 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.42
Residue 693: 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

Similar variants

NBAS c.1726-2A>G Likely pathogenic ★★ same type
NBAS c.173-2A>G Likely pathogenic ★★ same type
NBAS c.209+2T>G Pathogenic/Likely pathogenic ★★ same type
NBAS c.2423+404G>C Likely pathogenic ★★ same type
NBAS c.335+1G>C Pathogenic/Likely pathogenic ★★ same type
NBAS c.4461+2T>C Likely pathogenic ★★ same type
NBAS c.4583-2A>G Likely pathogenic ★★ same type
NBAS c.513+2T>C Pathogenic/Likely pathogenic ★★ same type

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-asp693 (accessed [today's date]).

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