Is STEEP1 p.Pro82Ala (c.244C>G) pathogenic?

STEEP1 p.Pro82Ala (c.244C>G) is classified Uncertain significance in STEEP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-08). AlphaMissense: likely benign (0.0529); Very rare (popmax 0.00299%, eas); Associated with intellectual disability, X-linked 107.

What condition is associated with STEEP1 p.Pro82Ala (c.244C>G)?

STEEP1 p.Pro82Ala (c.244C>G) is associated with intellectual disability, X-linked 107 (ClinVar).

How common is STEEP1 p.Pro82Ala (c.244C>G) in the general population?

STEEP1 p.Pro82Ala (c.244C>G) is very rare (popmax 0.00299%, eas) (gnomAD).

What do computational predictors say about STEEP1 p.Pro82Ala (c.244C>G)?

AlphaMissense predicts likely benign (score 0.0529) — an in-silico prediction, not a clinical call.

STEEP1 p.Pro82Ala

c.244C>G · VCV4279749

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0529 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00299%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability, X-linked 107

Computational evidence

Protein change
AlphaMissense	0.0529	likely benign
REVEL	0.176	moderately benign-leaning
SaProt	LLR -6.33	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.6	GERP 0.88, phastCons 1
Regional constraint	o/e 0.40	unconstrained · MANE · 23 kb · p 5.1e-11 · regional, not allelic
Overall
CADD	15.48	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00299% East Asian · 1/33,396 alleles

Overall 8.62e-05% 1/1,160,636 alleles · very rare exomes 1/1,047,150 · genomes 0/113,486 · 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: STEEP1
Protein: p.Pro82Ala
Coding: c.244C>G
MANE Select: NM_022101
Type: single nucleotide variant
Location: chrX:119545503 (GRCh38)
Structure: AlphaFold pLDDT 76.15 · 2 PDB

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

Disease context

intellectual disability, X-linked 107 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

STEEP1 c.-2T>C Benign ★★ same condition
STEEP1 p.Gly125= Benign ★★ same condition
STEEP1 p.Arg15Leu Uncertain significance ★ ⚠ same condition
STEEP1 p.Arg198Gln Uncertain significance ★ ⚠ same condition
STEEP1 p.Arg53Leu Uncertain significance ★ ⚠ same condition
STEEP1 p.Arg57Gly Uncertain significance ★ ⚠ same condition
STEEP1 p.Cys96Tyr Uncertain significance ★ ⚠ same condition
STEEP1 p.Gln200Ter Pathogenic same condition

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-pro82ala (accessed [today's date]).

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