Is ASNS p.Lys232Glu (c.694A>G) pathogenic?

ASNS p.Lys232Glu (c.694A>G) is classified Uncertain significance in ASNS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-17). AlphaMissense: likely benign (0.3266); Very rare (popmax 8.48e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ASNS p.Lys232Glu (c.694A>G)?

ASNS p.Lys232Glu (c.694A>G) is associated with Inborn genetic diseases (ClinVar).

How common is ASNS p.Lys232Glu (c.694A>G) in the general population?

ASNS p.Lys232Glu (c.694A>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about ASNS p.Lys232Glu (c.694A>G)?

AlphaMissense predicts likely benign (score 0.3266) — an in-silico prediction, not a clinical call.

ASNS p.Lys232Glu

c.694A>G · rs1791584965 · VCV2543734

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3266 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3266	likely benign
REVEL	0.162	moderately benign-leaning
SaProt	LLR -13.39	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.35 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.8	GERP 0.69, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 17 kb · p 5.1e-10 · regional, not allelic
Overall
CADD	22.8	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 8.48e-05% European (non-Finnish) · 1/1,179,858 alleles

Overall 6.84e-05% 1/1,461,018 alleles · very rare

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.Lys232Glu
Coding: c.694A>G
MANE Select: NM_001673
dbSNP: rs1791584965
Type: single nucleotide variant
Location: chr7:97858935 (GRCh38)
Gene constraint: LOEUF 0.745 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.36 · 3 PDB
Residue 232: the asparagine synthetase domain; an α-helix

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-lys232glu (accessed [today's date]).

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