Is ASNS p.Leu238Phe (c.712C>T) pathogenic?

ASNS p.Leu238Phe (c.712C>T) is classified Uncertain significance in ASNS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-15). AlphaMissense: ambiguous (0.5007); Absent from gnomAD v4.1.

How common is ASNS p.Leu238Phe (c.712C>T) in the general population?

ASNS p.Leu238Phe (c.712C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ASNS p.Leu238Phe (c.712C>T)?

AlphaMissense predicts ambiguous (score 0.5007) — an in-silico prediction, not a clinical call.

ASNS p.Leu238Phe

c.712C>T · rs1791584426 · VCV1933198

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5007 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.5007	ambiguous
REVEL	0.367	indeterminate
SaProt	LLR -11.62	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 17 kb · p 5.1e-10 · regional, not allelic
Overall
CADD	28.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ASNS
Protein: p.Leu238Phe
Coding: c.712C>T
MANE Select: NM_001673
dbSNP: rs1791584426
Type: single nucleotide variant
Location: chr7:97858917 (GRCh38)
Gene constraint: LOEUF 0.745 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.36 · 3 PDB
Residue 238: the asparagine synthetase domain; an α-helix

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

Similar variants

ASNS p.Leu238Ile Uncertain significance ★ ⚠ same residue
ASNS p.Leu238= Likely benign ★ same residue
ASNS c.1030+1G>A Likely pathogenic ★★ same type
ASNS c.1138-1G>A Likely pathogenic ★★ same type
ASNS c.1239-2A>T Likely pathogenic ★★ same type
ASNS c.1320+1G>C Likely pathogenic ★★ same type
ASNS c.1320+1G>T Likely pathogenic ★★ same type
ASNS c.1321-1G>A Likely pathogenic ★★ 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/asns-p-leu238phe (accessed [today's date]).

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