Is ASPNAT p.Leu32= (c.96C>T) pathogenic?

ASPNAT p.Leu32= (c.96C>T) is classified Benign in ASPNAT (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-10). Common (popmax 15.8%, eas) — too common for a highly-penetrant pathogenic allele; Associated with NAT8L-related disorder.

What condition is associated with ASPNAT p.Leu32= (c.96C>T)?

ASPNAT p.Leu32= (c.96C>T) is associated with NAT8L-related disorder (ClinVar).

ASPNAT p.Leu32=

Q: How common is ASPNAT p.Leu32= (c.96C>T) in the general population?

ASPNAT p.Leu32= (c.96C>T) is common (popmax 15.8%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.96C>T · rs183901937 · VCV3060891

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 15.8%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

NAT8L-related disorder

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 0.25	GERP 0.58, phastCons 0.97
Overall
CADD	13.06	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 15.8% East Asian · 1,347/8,544 alleles

Filtering AF 15.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 14.8%

Overall 2.2% 21,525/979,798 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	15.8%	6
Finnishnot grpmax-eligible	7.16%	14
Remaining individualsnot grpmax-eligible	2.72%	37
Admixed American	2.6%	39
European (non-Finnish)	2.15%	47
Ashkenazi Jewishnot grpmax-eligible	1.8%	56
Middle Eastern	1.22%	82
South Asian	1.07%	94
African / African-American	0.308%	325
Amishnot grpmax-eligible	0.226%	443

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: ASPNAT
Protein: p.Leu32=
Coding: c.96C>T
MANE Select: NM_178557
dbSNP: rs183901937
Type: single nucleotide variant
Location: chr4:2059607 (GRCh38)
Structure: AlphaFold pLDDT 81.36

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

Disease context

NAT8L-related disorder

Similar variants

ASPNAT p.Leu32Arg Uncertain significance ★ ⚠ same residue
ASPNAT c.541+7C>T Likely benign same condition
ASPNAT c.541+8C>T Benign ★★ same type
ASPNAT p.Ala35= Likely benign ★★ same type
ASPNAT p.Gly263= Likely benign ★★ same type
ASPNAT p.Pro56= Likely benign ★★ same type
ASPNAT p.Ala125Thr Uncertain significance ★ ⚠ same type
ASPNAT p.Ala225Thr Uncertain significance ★ ⚠ 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/aspnat-p-leu32 (accessed [today's date]).

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