Is STEAP3 p.Ser93Pro (c.277T>C) pathogenic?

STEAP3 p.Ser93Pro (c.277T>C) is classified Uncertain significance in STEAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-09). AlphaMissense: likely benign (0.163); Absent from gnomAD v4.1.

How common is STEAP3 p.Ser93Pro (c.277T>C) in the general population?

STEAP3 p.Ser93Pro (c.277T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about STEAP3 p.Ser93Pro (c.277T>C)?

AlphaMissense predicts likely benign (score 0.163) — an in-silico prediction, not a clinical call.

STEAP3 p.Ser93Pro

c.277T>C · VCV4176509

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.163 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.163	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -7.17	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.046	GERP -3.5
Regional constraint	o/e 0.98	unconstrained · MANE · 32 kb · p 0.55 · regional, not allelic
Overall
CADD	16.17	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S83P vs ClinVar S93P) — verify the residue.

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: STEAP3
Protein: p.Ser93Pro
Coding: c.277T>C
MANE Select: NM_182915
Type: single nucleotide variant
Location: chr2:119245743 (GRCh38)
Gene constraint: LOEUF 1.27 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.24 · 2 PDB

Full STEAP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

STEAP3 p.Ala490Thr Uncertain significance ★★ ⚠ same type
STEAP3 p.Arg217Ser Uncertain significance ★★ ⚠ same type
STEAP3 p.Arg293Trp Uncertain significance ★★ ⚠ same type
STEAP3 p.Arg336His Uncertain significance ★★ ⚠ same type
STEAP3 p.Arg466Cys Uncertain significance ★★ ⚠ same type
STEAP3 p.Gln87Arg Uncertain significance ★★ ⚠ same type
STEAP3 p.Glu141Lys Uncertain significance ★★ ⚠ same type
STEAP3 p.Gly379Cys 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/steap3-p-ser93pro (accessed [today's date]).

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