Is ASAP1 p.Thr803Pro (c.2407A>C) pathogenic?

ASAP1 p.Thr803Pro (c.2407A>C) is classified Uncertain significance in ASAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-31). AlphaMissense: likely benign (0.0546); Very rare (popmax 8.6e-05%, nfe).

How common is ASAP1 p.Thr803Pro (c.2407A>C) in the general population?

ASAP1 p.Thr803Pro (c.2407A>C) is very rare (popmax 8.6e-05%, nfe) (gnomAD).

What do computational predictors say about ASAP1 p.Thr803Pro (c.2407A>C)?

AlphaMissense predicts likely benign (score 0.0546) — an in-silico prediction, not a clinical call.

ASAP1 p.Thr803Pro

c.2407A>C · VCV3788022

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0546 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.6e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0546	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -5.49	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.34	GERP -4.6, phastCons 0.16
Regional constraint	o/e 0.94	unconstrained · MANE · 39 kb · p 0.25 · regional, not allelic
Overall
CADD	16.67	PHRED · no single calibrated threshold — expert panels disagree

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

Grpmax group 8.6e-05% European (non-Finnish) · 1/1,162,172 alleles

Overall 7.08e-05% 1/1,412,514 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: ASAP1
Protein: p.Thr803Pro
Coding: c.2407A>C
MANE Select: NM_018482
Type: single nucleotide variant
Location: chr8:130092138 (GRCh38)
Gene constraint: LOEUF 0.439 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.05 · 5 PDB
Residue 803: the 'disordered' region

Full ASAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASAP1 p.Gln263= Benign ★★ same type
ASAP1 p.Ala1035Gly Uncertain significance ★ ⚠ same type
ASAP1 p.Ala429Val Uncertain significance ★ ⚠ same type
ASAP1 p.Ala914Gly Uncertain significance ★ ⚠ same type
ASAP1 p.Arg212His Uncertain significance ★ ⚠ same type
ASAP1 p.Arg447Gln Uncertain significance ★ ⚠ same type
ASAP1 p.Arg710Ter Uncertain significance ★ same type
ASAP1 p.Arg764Gln 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/asap1-p-thr803pro (accessed [today's date]).

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