Is STEAP3 p.Arg427Pro (c.1280G>C) pathogenic?

STEAP3 p.Arg427Pro (c.1280G>C) is classified Uncertain significance in STEAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-29). AlphaMissense: likely pathogenic (0.8057); Ultra-rare (popmax 0.0156%, eas).

How common is STEAP3 p.Arg427Pro (c.1280G>C) in the general population?

STEAP3 p.Arg427Pro (c.1280G>C) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

What do computational predictors say about STEAP3 p.Arg427Pro (c.1280G>C)?

AlphaMissense predicts likely pathogenic (score 0.8057) — an in-silico prediction, not a clinical call.

STEAP3 p.Arg427Pro

c.1280G>C · rs772740148 · VCV2531135

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8057 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8057	likely pathogenic
REVEL	0.267	benign-leaning
SaProt	LLR -12.71	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 8.6	GERP 2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 32 kb · p 0.55 · regional, not allelic
Overall
CADD	28.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R417P vs ClinVar R427P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0156% East Asian · 7/44,880 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.000434% 7/1,613,044 alleles · ultra-rare exomes 3/1,460,748 · genomes 4/152,296 · joint denominator

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: STEAP3
Protein: p.Arg427Pro
Coding: c.1280G>C
MANE Select: NM_182915
dbSNP: rs772740148
Type: single nucleotide variant
Location: chr2:119263121 (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.Arg427Cys Uncertain significance ★ ⚠ same residue
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

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-arg427pro (accessed [today's date]).

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