Is ASNS p.Val359Met (c.1075G>A) pathogenic?

ASNS p.Val359Met (c.1075G>A) is classified Uncertain significance in ASNS (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-11-15). AlphaMissense: likely benign (0.2984); Very rare (popmax 0.00297%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ASNS p.Val359Met (c.1075G>A)?

ASNS p.Val359Met (c.1075G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ASNS p.Val359Met (c.1075G>A) in the general population?

ASNS p.Val359Met (c.1075G>A) is very rare (popmax 0.00297%, nfe) (gnomAD).

What do computational predictors say about ASNS p.Val359Met (c.1075G>A)?

AlphaMissense predicts likely benign (score 0.2984) — an in-silico prediction, not a clinical call.

ASNS p.Val359Met

c.1075G>A · rs374069172 · VCV2201386

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.2984 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00297%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2984	likely benign
REVEL	0.235	benign-leaning
SaProt	LLR -9.53	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 17 kb · p 5.1e-10 · regional, not allelic
Overall
CADD	26.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00297% European (non-Finnish) · 35/1,179,546 alleles

Filtering AF 0.00215% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00191%

Overall 0.00242% 39/1,612,248 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00297%	33,701
African / African-American	0.00267%	37,438
East Asian	0.00223%	44,848
South Asian	0.0011%	90,966

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: ASNS
Protein: p.Val359Met
Coding: c.1075G>A
MANE Select: NM_001673
dbSNP: rs374069172
Type: single nucleotide variant
Location: chr7:97855415 (GRCh38)
Gene constraint: LOEUF 0.745 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.36 · 3 PDB
Residue 359: the asparagine synthetase domain; a β-strand

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ASNS c.1320+1G>C Likely pathogenic ★★ same condition
ASNS p.Arg465Ter Pathogenic/Likely pathogenic ★★ same condition
ASNS p.Arg550His Pathogenic/Likely pathogenic ★★ ⚠ same condition
ASNS c.1238+3A>G Uncertain significance ★★ same condition
ASNS p.Ala303Glu Uncertain significance ★★ ⚠ same condition
ASNS p.Arg251Gly Uncertain significance ★★ ⚠ same condition
ASNS p.Arg392Lys Uncertain significance ★★ ⚠ same condition
ASNS p.Asn441Ser 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/asns-p-val359met (accessed [today's date]).

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