Is ASNS p.His81Pro (c.242A>C) pathogenic?

ASNS p.His81Pro (c.242A>C) is classified Uncertain significance in ASNS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-03). AlphaMissense: likely pathogenic (0.6039); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ASNS p.His81Pro (c.242A>C)?

ASNS p.His81Pro (c.242A>C) is associated with Inborn genetic diseases (ClinVar).

How common is ASNS p.His81Pro (c.242A>C) in the general population?

ASNS p.His81Pro (c.242A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ASNS p.His81Pro (c.242A>C)?

AlphaMissense predicts likely pathogenic (score 0.6039) — an in-silico prediction, not a clinical call.

ASNS p.His81Pro

c.242A>C · VCV4586272

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6039 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6039	likely pathogenic
REVEL	0.304	indeterminate
SaProt	LLR -13.13	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 17 kb · p 5.1e-10 · regional, not allelic
Overall
CADD	23.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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.His81Pro
Coding: c.242A>C
MANE Select: NM_001673
Type: single nucleotide variant
Location: chr7:97868915 (GRCh38)
Gene constraint: LOEUF 0.745 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.36 · 3 PDB
Residue 81: the glutamine amidotransferase type-2 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 p.His81Arg Uncertain significance ★ ⚠ same residue
ASNS p.His81= Likely benign ★ same residue
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

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-his81pro (accessed [today's date]).

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