Is ASPNAT p.Ile224= (c.672C>T) pathogenic?

ASPNAT p.Ile224= (c.672C>T) is classified Likely benign in ASPNAT (ClinVar, Single submitter, 1 submitter; last evaluated 2018-10-10). Ultra-rare (popmax 0.0165%, mid).

How common is ASPNAT p.Ile224= (c.672C>T) in the general population?

ASPNAT p.Ile224= (c.672C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

ASPNAT p.Ile224=

c.672C>T · rs374871366 · VCV792279

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

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	GERP -4.7
Overall
CADD	7.806	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,076 alleles

Filtering AF 0.00207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00183%

Overall 0.00236% 38/1,612,242 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,076
Remaining individualsnot grpmax-eligible	0.0032%	31,227
European (non-Finnish)	0.00288%	34,705
Finnishnot grpmax-eligible	0.0016%	62,342

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.Ile224=
Coding: c.672C>T
MANE Select: NM_178557
dbSNP: rs374871366
Type: single nucleotide variant
Location: chr4:2063890 (GRCh38)
Structure: AlphaFold pLDDT 81.36
Residue 224: the n-acetyltransferase domain

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

Similar variants

ASPNAT p.Ile224Leu Uncertain significance ★ ⚠ same residue
ASPNAT p.Ile224Val Uncertain significance ★ ⚠ same residue
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-ile224 (accessed [today's date]).

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