Is ASAP1 p.Thr178Ile (c.533C>T) pathogenic?

ASAP1 p.Thr178Ile (c.533C>T) is classified Uncertain significance in ASAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-17). AlphaMissense: ambiguous (0.3787); Absent from gnomAD v4.1.

How common is ASAP1 p.Thr178Ile (c.533C>T) in the general population?

ASAP1 p.Thr178Ile (c.533C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ASAP1 p.Thr178Ile (c.533C>T)?

AlphaMissense predicts ambiguous (score 0.3787) — an in-silico prediction, not a clinical call.

ASAP1 p.Thr178Ile

c.533C>T · VCV3950575

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3787 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,601,892)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3787	ambiguous
REVEL	0.244	benign-leaning
SaProt	LLR -8.91	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.89 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.48	unconstrained · MANE · 35 kb · p 6e-11 · regional, not allelic
Overall
CADD	32.0	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

No allele count reported in gnomAD v4.1 (AN 1,601,892). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ASAP1
Protein: p.Thr178Ile
Coding: c.533C>T
MANE Select: NM_018482
Type: single nucleotide variant
Location: chr8:130180878 (GRCh38)
Gene constraint: LOEUF 0.439 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.05 · 5 PDB

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-thr178ile (accessed [today's date]).

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