Is STRADA p.Ile305Val (c.913A>G) pathogenic?

STRADA p.Ile305Val (c.913A>G) is classified Uncertain significance in STRADA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-16). AlphaMissense: likely benign (0.2114); Very rare (popmax 0.00275%, afr); Associated with Inborn genetic diseases.

What condition is associated with STRADA p.Ile305Val (c.913A>G)?

STRADA p.Ile305Val (c.913A>G) is associated with Inborn genetic diseases, polyhydramnios, megalencephaly, and symptomatic epilepsy (ClinVar).

How common is STRADA p.Ile305Val (c.913A>G) in the general population?

STRADA p.Ile305Val (c.913A>G) is very rare (popmax 0.00275%, afr) (gnomAD).

What do computational predictors say about STRADA p.Ile305Val (c.913A>G)?

AlphaMissense predicts likely benign (score 0.2114) — an in-silico prediction, not a clinical call.

STRADA p.Ile305Val

c.913A>G · rs2035943068 · VCV1370537

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2114 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00275%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2114	likely benign
REVEL	0.162	moderately benign-leaning
SaProt	LLR -5.84	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP -0.78, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 25 kb · p 5.3e-06 · regional, not allelic
Overall
CADD	19.79	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 0.00275% African / African-American · 2/72,846 alleles

Filtering AF 0.000456% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000171%

Overall 0.000126% 2/1,583,744 alleles · very rare exomes 1/1,437,006 · genomes 1/146,738 · 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: STRADA
Protein: p.Ile305Val
Coding: c.913A>G
MANE Select: NM_001003787
dbSNP: rs2035943068
Type: single nucleotide variant
Location: chr17:63704528 (GRCh38)
Gene constraint: LOEUF 0.649 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.46 · 4 PDB
Residue 305: the protein kinase domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: polyhydramnios, megalencephaly, and symptomatic epilepsy

Similar variants

STRADA c.36+1G>A Likely pathogenic ★★ same condition
STRADA c.37-1G>C Likely pathogenic ★★ same condition
STRADA p.Arg228Ter Pathogenic ★★ same condition
STRADA p.Ala45Val Uncertain significance ★★ ⚠ same condition
STRADA p.Arg100Gln Uncertain significance ★★ ⚠ same condition
STRADA p.Arg13Gln Uncertain significance ★★ same condition
STRADA p.Arg13Leu Uncertain significance ★★ ⚠ same condition
STRADA p.Arg13Trp Uncertain significance ★★ ⚠ 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/strada-p-ile305val (accessed [today's date]).

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