Is STRADB p.Leu289Phe (c.867G>T) pathogenic?

STRADB p.Leu289Phe (c.867G>T) is classified Uncertain significance in STRADB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-30). AlphaMissense: likely benign (0.0798); Absent from gnomAD v4.1.

How common is STRADB p.Leu289Phe (c.867G>T) in the general population?

STRADB p.Leu289Phe (c.867G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about STRADB p.Leu289Phe (c.867G>T)?

AlphaMissense predicts likely benign (score 0.0798) — an in-silico prediction, not a clinical call.

STRADB p.Leu289Phe

c.867G>T · VCV3963566

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0798 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0798	likely benign
REVEL	0.141	moderately benign-leaning
SaProt	LLR -6.77	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.49	acceptor gain · deltas
Pangolin	Δ0.48	gain · loss 0.32 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 5	GERP 2, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 25 kb · p 6e-11 · regional, not allelic
Overall
CADD	26.3	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

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: STRADB
Protein: p.Leu289Phe
Coding: c.867G>T
MANE Select: NM_018571
Type: single nucleotide variant
Location: chr2:201478398 (GRCh38)
Gene constraint: LOEUF 0.792 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.39
Residue 289: the protein kinase domain

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

Similar variants

STRADB p.Ala103Pro Uncertain significance ★ ⚠ same type
STRADB p.Ala46Val Uncertain significance ★ ⚠ same type
STRADB p.Arg100Cys Uncertain significance ★ ⚠ same type
STRADB p.Arg100Leu Uncertain significance ★ ⚠ same type
STRADB p.Arg115Trp Uncertain significance ★ ⚠ same type
STRADB p.Arg329Gln Uncertain significance ★ ⚠ same type
STRADB p.Arg41Cys Uncertain significance ★ ⚠ same type
STRADB p.Asn163Ser 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/stradb-p-leu289phe (accessed [today's date]).

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