Is ASPNAT p.Val188Met (c.562G>A) pathogenic?

ASPNAT p.Val188Met (c.562G>A) is classified Uncertain significance in ASPNAT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-07). AlphaMissense: ambiguous (0.3756); Ultra-rare (popmax 0.0111%, eas).

How common is ASPNAT p.Val188Met (c.562G>A) in the general population?

ASPNAT p.Val188Met (c.562G>A) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

What do computational predictors say about ASPNAT p.Val188Met (c.562G>A)?

AlphaMissense predicts ambiguous (score 0.3756) — an in-silico prediction, not a clinical call.

ASPNAT p.Val188Met

c.562G>A · rs775990289 · VCV3176619

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3756 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3756	ambiguous
REVEL	0.231	benign-leaning
SaProt	LLR -8.29	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.3, phastCons 1
Regional constraint	o/e 0.56	unconstrained · MANE · 3,077 bp · p 8.6e-12 · regional, not allelic
Overall
CADD	29.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0111% East Asian · 5/44,898 alleles

Filtering AF 0.00546% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00506%

Overall 0.00627% 101/1,611,818 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0194%	5,160
East Asiangrpmax	0.0111%	8,980
European (non-Finnish)	0.0067%	14,936
Remaining individualsnot grpmax-eligible	0.0032%	31,224
South Asian	0.0022%	45,542
Admixed American	0.00167%	60,012

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val188Met
Coding: c.562G>A
MANE Select: NM_178557
dbSNP: rs775990289
Type: single nucleotide variant
Location: chr4:2063780 (GRCh38)
Structure: AlphaFold pLDDT 81.36
Residue 188: the n-acetyltransferase domain

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

Similar variants

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
ASPNAT p.Ala22Val Uncertain significance ★ ⚠ same type
ASPNAT p.Ala255Thr 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-val188met (accessed [today's date]).

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