Is ASPA p.Asn97Lys (c.291T>A) pathogenic?

ASPA p.Asn97Lys (c.291T>A) is classified Uncertain significance in ASPA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-13). AlphaMissense: likely pathogenic (0.6602); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ASPA p.Asn97Lys (c.291T>A)?

ASPA p.Asn97Lys (c.291T>A) is associated with Inborn genetic diseases (ClinVar).

How common is ASPA p.Asn97Lys (c.291T>A) in the general population?

ASPA p.Asn97Lys (c.291T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ASPA p.Asn97Lys (c.291T>A)?

AlphaMissense predicts likely pathogenic (score 0.6602) — an in-silico prediction, not a clinical call.

ASPA p.Asn97Lys

c.291T>A · VCV3953075

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6602 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6602	likely pathogenic
REVEL	0.79	moderately pathogenic-leaning
SaProt	LLR -10.80	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.52	GERP -0.3, phastCons 0.24
Regional constraint	o/e 0.86	unconstrained · MANE · 23 kb · p 0.0073 · regional, not allelic
Overall
CADD	19.79	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: ASPA
Protein: p.Asn97Lys
Coding: c.291T>A
MANE Select: NM_000049
Type: single nucleotide variant
Location: chr17:3481657 (GRCh38)
Gene constraint: LOEUF 1.098 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.14 · 8 PDB
Residue 97: an α-helix

Full ASPA 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

ASPA p.Asn97Ser Uncertain significance ★★ ⚠ same residue
ASPA p.Asn97= Likely benign ★ same residue
ASPA p.Gln184Ter Pathogenic ★★ same condition
ASPA p.Arg92Ser Uncertain significance ★★ ⚠ same condition
ASPA p.Asp110His Uncertain significance ★★ ⚠ same condition
ASPA p.Lys163Gln Uncertain significance ★★ ⚠ same condition
ASPA p.Ala93= Likely benign ★★ same condition
ASPA p.His10= Likely benign ★★ 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/aspa-p-asn97lys (accessed [today's date]).

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