Is ASPG p.Thr19Pro (c.55A>C) pathogenic?

ASPG p.Thr19Pro (c.55A>C) is classified Uncertain significance in ASPG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-02). AlphaMissense: likely pathogenic (0.5656); Absent from gnomAD v4.1.

How common is ASPG p.Thr19Pro (c.55A>C) in the general population?

ASPG p.Thr19Pro (c.55A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ASPG p.Thr19Pro (c.55A>C)?

AlphaMissense predicts likely pathogenic (score 0.5656) — an in-silico prediction, not a clinical call.

ASPG p.Thr19Pro

c.55A>C · VCV4643523

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5656 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.5656	likely pathogenic
REVEL	0.574	indeterminate
SaProt	LLR -16.17	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 10	GERP 1.1, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 27 kb · p 0.058 · regional, not allelic
Overall
CADD	28.0	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: ASPG
Protein: p.Thr19Pro
Coding: c.55A>C
MANE Select: NM_001080464
Type: single nucleotide variant
Location: chr14:104085825 (GRCh38)
Gene constraint: LOEUF 1.226 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.05 · 2 PDB
Residue 19: the asparaginase/glutaminase domain; an active site

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

Similar variants

ASPG p.Asp223= Benign ★★ same type
ASPG c.1620+1G>A Uncertain significance ★ same type
ASPG p.Ala315Gly Uncertain significance ★ ⚠ same type
ASPG p.Ala315Val Uncertain significance ★ ⚠ same type
ASPG p.Ala332Val Uncertain significance ★ ⚠ same type
ASPG p.Ala442Thr Uncertain significance ★ ⚠ same type
ASPG p.Ala4Thr Uncertain significance ★ ⚠ same type
ASPG p.Ala537Ser Uncertain significance ★ ⚠ 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/aspg-p-thr19pro (accessed [today's date]).

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