Is STEEP1 p.Arg147Pro (c.440G>C) pathogenic?

STEEP1 p.Arg147Pro (c.440G>C) is classified Uncertain significance in STEEP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-18). AlphaMissense: likely pathogenic (0.9988); Absent from gnomAD v4.1.

How common is STEEP1 p.Arg147Pro (c.440G>C) in the general population?

STEEP1 p.Arg147Pro (c.440G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about STEEP1 p.Arg147Pro (c.440G>C)?

AlphaMissense predicts likely pathogenic (score 0.9988) — an in-silico prediction, not a clinical call.

STEEP1 p.Arg147Pro

c.440G>C · VCV3360184

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9988 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9988	likely pathogenic · top 10% in STEEP1
REVEL	0.323	indeterminate
SaProt	LLR -5.63	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.12	constrained · MANE · 2,850 bp · p 1.6e-11 · regional, not allelic
Overall
CADD	24.6	PHRED · no single calibrated threshold — expert panels disagree

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

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: STEEP1
Protein: p.Arg147Pro
Coding: c.440G>C
MANE Select: NM_022101
Type: single nucleotide variant
Location: chrX:119542578 (GRCh38)
Structure: AlphaFold pLDDT 76.15 · 2 PDB

Full STEEP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

STEEP1 c.-2T>C Benign ★★ same type
STEEP1 p.Gly125= Benign ★★ same type
STEEP1 c.243-4G>A Uncertain significance ★ same type
STEEP1 c.-50C>T Uncertain significance ★ same type
STEEP1 c.*595T>A Uncertain significance ★ same type
STEEP1 p.Arg15Leu Uncertain significance ★ ⚠ same type
STEEP1 p.Arg198Gln Uncertain significance ★ ⚠ same type
STEEP1 p.Arg53Leu 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/steep1-p-arg147pro (accessed [today's date]).

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