Is NAGA p.Arg90= (c.270C>T) pathogenic?

NAGA p.Arg90= (c.270C>T) is classified Likely benign in NAGA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-07). Very rare (popmax 0.00364%, nfe); Associated with alpha-N-acetylgalactosaminidase deficiency type 1.

What condition is associated with NAGA p.Arg90= (c.270C>T)?

NAGA p.Arg90= (c.270C>T) is associated with alpha-N-acetylgalactosaminidase deficiency type 1 (ClinVar).

How common is NAGA p.Arg90= (c.270C>T) in the general population?

NAGA p.Arg90= (c.270C>T) is very rare (popmax 0.00364%, nfe) (gnomAD).

How is Alpha-N-acetylgalactosaminidase deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

NAGA p.Arg90=

c.270C>T · rs547692110 · VCV2901462

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00364%, nfe)

Conditions

alpha-N-acetylgalactosaminidase deficiency type 1

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 1.4	GERP -3.7, phastCons 0.87
Overall
CADD	9.468	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00364% European (non-Finnish) · 43/1,179,952 alleles

Filtering AF 0.00275% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00244%

Overall 0.00279% 45/1,612,330 alleles · very rare exomes 40/1,460,236 · genomes 5/152,094 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00364%	27,441
Admixed American	0.00167%	60,004
Remaining individualsnot grpmax-eligible	0.0016%	62,454

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: NAGA
Protein: p.Arg90=
Coding: c.270C>T
MANE Select: NM_000262
dbSNP: rs547692110
Type: single nucleotide variant
Location: chr22:42067819 (GRCh38)
Gene constraint: LOEUF 1.121 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.18 · 7 PDB

Full NAGA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

alpha-N-acetylgalactosaminidase deficiency type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Alpha-N-acetylgalactosaminidase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Adult, Childhood, Infancy

Similar variants

NAGA p.Gln292Ter Pathogenic ★★ same condition
NAGA p.Trp148Ter Pathogenic/Likely pathogenic ★★ same condition
NAGA p.Ala268Thr Uncertain significance ★★ ⚠ same condition
NAGA p.Ala291Thr Uncertain significance ★★ ⚠ same condition
NAGA p.Arg165Trp Uncertain significance ★★ ⚠ same condition
NAGA p.Arg213His Uncertain significance ★★ ⚠ same condition
NAGA p.Arg37His Uncertain significance ★★ ⚠ same condition
NAGA p.Asn391Ser 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/naga-p-arg90 (accessed [today's date]).

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