Is NAGA p.Ser336= (c.1008C>T) pathogenic?

NAGA p.Ser336= (c.1008C>T) is classified Likely benign in NAGA (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-07). Ultra-rare (popmax 0.0164%, mid); Associated with alpha-N-acetylgalactosaminidase deficiency type 1.

What condition is associated with NAGA p.Ser336= (c.1008C>T)?

NAGA p.Ser336= (c.1008C>T) is associated with alpha-N-acetylgalactosaminidase deficiency type 1 (ClinVar).

How common is NAGA p.Ser336= (c.1008C>T) in the general population?

NAGA p.Ser336= (c.1008C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

How is Alpha-N-acetylgalactosaminidase deficiency inherited?

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

NAGA p.Ser336=

c.1008C>T · rs758171119 · VCV2172805

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

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 -4.9	GERP -3.1
Overall
CADD	2.066	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.00229% 37/1,614,074 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
African / African-American	0.00667%	14,988
Remaining individualsnot grpmax-eligible	0.0064%	15,622
Admixed American	0.00333%	30,002
South Asian	0.0022%	45,545
European (non-Finnish)	0.00186%	53,638
Finnishnot grpmax-eligible	0.00156%	64,024

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.Ser336=
Coding: c.1008C>T
MANE Select: NM_000262
dbSNP: rs758171119
Type: single nucleotide variant
Location: chr22:42061017 (GRCh38)
Gene constraint: LOEUF 1.121 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.18 · 7 PDB
Residue 336: a β-strand

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-ser336 (accessed [today's date]).

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