Is STAP1 p.Thr53Pro (c.157A>C) pathogenic?

STAP1 p.Thr53Pro (c.157A>C) is classified Uncertain significance in STAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-08). AlphaMissense: likely pathogenic (0.8931); Absent from gnomAD v4.1.

How common is STAP1 p.Thr53Pro (c.157A>C) in the general population?

STAP1 p.Thr53Pro (c.157A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about STAP1 p.Thr53Pro (c.157A>C)?

AlphaMissense predicts likely pathogenic (score 0.8931) — an in-silico prediction, not a clinical call.

STAP1 p.Thr53Pro

c.157A>C · rs1727595529 · VCV3226188

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8931 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8931	likely pathogenic
REVEL	0.705	pathogenic-leaning
SaProt	LLR -16.04	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 9	GERP 1.4, phastCons 1
Overall
CADD	24.2	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: STAP1
Protein: p.Thr53Pro
Coding: c.157A>C
MANE Select: NM_012108
dbSNP: rs1727595529
Type: single nucleotide variant
Location: chr4:67571120 (GRCh38)
Structure: AlphaFold pLDDT 88.06

Full STAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

STAP1 p.Thr53Ile Uncertain significance ★ ⚠ same residue
STAP1 p.Thr53= Likely benign ★ same residue
STAP1 p.Gln192Arg Uncertain significance ★★ ⚠ same type
STAP1 p.Leu288Val Uncertain significance ★★ ⚠ same type
STAP1 c.120+6T>C Benign/Likely benign ★★ same type
STAP1 c.192+102T>C Likely benign ★★ same type
STAP1 c.192+10T>C Benign ★★ same type
STAP1 c.530+11A>G Benign ★★ 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/stap1-p-thr53pro (accessed [today's date]).

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