Is NAGA p.Phe232= (c.696C>T) pathogenic?

NAGA p.Phe232= (c.696C>T) is classified Likely benign in NAGA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-20). Ultra-rare (popmax 0.0165%, mid); Associated with alpha-N-acetylgalactosaminidase deficiency type 1.

What condition is associated with NAGA p.Phe232= (c.696C>T)?

NAGA p.Phe232= (c.696C>T) is associated with alpha-N-acetylgalactosaminidase deficiency type 1 (ClinVar).

How common is NAGA p.Phe232= (c.696C>T) in the general population?

NAGA p.Phe232= (c.696C>T) is ultra-rare (popmax 0.0165%, 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.Phe232=

c.696C>T · rs572342989 · VCV3017001

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, 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.
REVEL	0.028	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.32 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.41	GERP -2.5
Overall
CADD	4.37	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000434% 7/1,614,098 alleles · ultra-rare exomes 5/1,461,870 · genomes 2/152,228 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
Admixed American	0.005%	20,007
East Asian	0.00223%	44,860
South Asian	0.0011%	91,076
European (non-Finnish)	8.47e-05%	1,180,040

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.Phe232=
Coding: c.696C>T
MANE Select: NM_000262
dbSNP: rs572342989
Type: single nucleotide variant
Location: chr22:42065801 (GRCh38)
Gene constraint: LOEUF 1.121 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.18 · 7 PDB
Residue 232: an α-helix

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-phe232 (accessed [today's date]).

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