Is STEAP3 p.Pro35= (c.105C>T) pathogenic?

STEAP3 p.Pro35= (c.105C>T) is classified Likely benign in STEAP3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-08-07). Very rare (popmax 0.00167%, amr); Associated with STEAP3-related disorder.

What condition is associated with STEAP3 p.Pro35= (c.105C>T)?

STEAP3 p.Pro35= (c.105C>T) is associated with STEAP3-related disorder (ClinVar).

How common is STEAP3 p.Pro35= (c.105C>T) in the general population?

STEAP3 p.Pro35= (c.105C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

STEAP3 p.Pro35=

c.105C>T · rs1573558431 · VCV3031037

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

STEAP3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.15	GERP -0.95
Overall
CADD	9.331	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,884 alleles

Filtering AF 0.000431% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000314%

Overall 0.000747% 12/1,605,946 alleles · very rare exomes 10/1,453,730 · genomes 2/152,216 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,884
Remaining individualsnot grpmax-eligible	0.00161%	62,022
European (non-Finnish)	0.000852%	117,339

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.Pro35=
Coding: c.105C>T
MANE Select: NM_182915
dbSNP: rs1573558431
Type: single nucleotide variant
Location: chr2:119245571 (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

Disease context

STEAP3-related disorder

Similar variants

STEAP3 c.1215+2650C>A Likely benign same condition
STEAP3 c.1215+2737C>T Benign same condition
STEAP3 c.1215+2773A>T Benign same condition
STEAP3 p.Ala117= Likely benign same condition
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

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-pro35 (accessed [today's date]).

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