Is STEAP3 p.Ser27= (c.81C>T) pathogenic?

STEAP3 p.Ser27= (c.81C>T) is classified Likely benign in STEAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-01). Very rare (popmax 0.00899%, eas).

How common is STEAP3 p.Ser27= (c.81C>T) in the general population?

STEAP3 p.Ser27= (c.81C>T) is very rare (popmax 0.00899%, eas) (gnomAD).

STEAP3 p.Ser27=

c.81C>T · rs141153214 · VCV2651296

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00899%, eas)

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 -8.3	GERP -2.5
Overall
CADD	0.269	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00899% East Asian · 4/44,482 alleles

Filtering AF 0.0032% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00289%

Overall 0.00443% 71/1,601,790 alleles · very rare exomes 64/1,449,454 · genomes 7/152,336 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0129%	7,730
East Asiangrpmax	0.00899%	11,121
Admixed American	0.00502%	19,937
European (non-Finnish)	0.00419%	23,878
African / African-American	0.00401%	24,947
South Asian	0.0033%	30,263
Finnishnot grpmax-eligible	0.00157%	63,578

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser27=
Coding: c.81C>T
MANE Select: NM_182915
dbSNP: rs141153214
Type: single nucleotide variant
Location: chr2:119245547 (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-ser27 (accessed [today's date]).

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