Is STAT5B p.Val435= (c.1305G>A) pathogenic?

STAT5B p.Val435= (c.1305G>A) is classified Likely benign in STAT5B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-10-06). Absent from gnomAD v4.1; Associated with STAT5B-related disorder.

What condition is associated with STAT5B p.Val435= (c.1305G>A)?

STAT5B p.Val435= (c.1305G>A) is associated with STAT5B-related disorder (ClinVar).

How common is STAT5B p.Val435= (c.1305G>A) in the general population?

STAT5B p.Val435= (c.1305G>A) is absent from gnomAD v4.1 (gnomAD).

STAT5B p.Val435=

c.1305G>A · rs2508749885 · VCV3032940

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

STAT5B-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.3	GERP -4.2
Overall
CADD	7.242	PHRED · no single calibrated threshold — expert panels disagree

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: STAT5B
Protein: p.Val435=
Coding: c.1305G>A
MANE Select: NM_012448
dbSNP: rs2508749885
Type: single nucleotide variant
Location: chr17:42217235 (GRCh38)
Gene constraint: LOEUF 0.277 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.90 · 2 PDB
Residue 435: a turn

Full STAT5B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

STAT5B-related disorder

Similar variants

STAT5B p.Arg226Cys Uncertain significance ★★ ⚠ same condition
STAT5B p.Val362Met Uncertain significance ★★ ⚠ same condition
STAT5B p.Gln703Ter Likely pathogenic ★ same condition
STAT5B c.1258-5T>C Uncertain significance ★ same condition
STAT5B p.Ile285Val Uncertain significance ★ ⚠ same condition
STAT5B p.Asn477Ser Uncertain significance same condition
STAT5B p.Asn96His Uncertain significance ⚠ same condition
STAT5B p.Gly596= Likely benign 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/stat5b-p-val435 (accessed [today's date]).

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