Is STEAP3 p.Val414Met (c.1240G>A) pathogenic?

STEAP3 p.Val414Met (c.1240G>A) is classified Uncertain significance in STEAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-10). AlphaMissense: likely benign (0.1311); Ultra-rare (popmax 0.0187%, mid).

How common is STEAP3 p.Val414Met (c.1240G>A) in the general population?

STEAP3 p.Val414Met (c.1240G>A) is ultra-rare (popmax 0.0187%, mid) (gnomAD).

What do computational predictors say about STEAP3 p.Val414Met (c.1240G>A)?

AlphaMissense predicts likely benign (score 0.1311) — an in-silico prediction, not a clinical call.

STEAP3 p.Val414Met

c.1240G>A · rs1473184416 · VCV2985557

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1311 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1311	likely benign
REVEL	0.072	moderately benign-leaning
SaProt	LLR -10.11	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.9	GERP -3, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 32 kb · p 0.55 · regional, not allelic
Overall
CADD	19.79	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 V404M vs ClinVar V414M) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0187% Middle Eastern · 1/5,338 alleles

Filtering AF 0.00386% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00353%

Overall 0.00392% 63/1,608,044 alleles · ultra-rare exomes 61/1,455,990 · genomes 2/152,054 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0187%	5,338
European (non-Finnish)	0.00492%	20,344
African / African-American	0.00267%	37,429
Admixed American	0.00167%	59,986
South Asian	0.0011%	91,022

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.Val414Met
Coding: c.1240G>A
MANE Select: NM_182915
dbSNP: rs1473184416
Type: single nucleotide variant
Location: chr2:119263081 (GRCh38)
Gene constraint: LOEUF 1.27 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.24 · 2 PDB
Residue 404 UniProt numbering: the ferric oxidoreductase domain

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

Similar variants

STEAP3 p.Val414Ala 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-val414met (accessed [today's date]).

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