Is STAT5B p.Val712Glu (c.2135T>A) pathogenic?

STAT5B p.Val712Glu (c.2135T>A) is classified Uncertain significance in STAT5B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-17). AlphaMissense: likely benign (0.3369); No allele count reported in gnomAD v4.1 (AN 1,614,112); Associated with growth hormone insensitivity with immune dysregulation 1, autosomal recessive.

What condition is associated with STAT5B p.Val712Glu (c.2135T>A)?

STAT5B p.Val712Glu (c.2135T>A) is associated with growth hormone insensitivity with immune dysregulation 1, autosomal recessive (ClinVar).

How common is STAT5B p.Val712Glu (c.2135T>A) in the general population?

STAT5B p.Val712Glu (c.2135T>A) is no allele count reported in gnomAD v4.1 (AN 1,614,112) (gnomAD).

How is Laron syndrome with immunodeficiency inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about STAT5B p.Val712Glu (c.2135T>A)?

AlphaMissense predicts likely benign (score 0.3369) — an in-silico prediction, not a clinical call.

STAT5B p.Val712Glu

c.2135T>A · VCV3688131

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3369 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,614,112)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

growth hormone insensitivity with immune dysregulation 1, autosomal recessive

Computational evidence

Protein change
AlphaMissense	0.3369	likely benign
REVEL	0.218	benign-leaning
SaProt	LLR -6.18	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 4	GERP -1.7, phastCons 1
Regional constraint	o/e 0.04	constrained · MANE · 366 bp · p 4.2e-06 · regional, not allelic
Overall
CADD	20.4	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

No allele count reported in gnomAD v4.1 (AN 1,614,112). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: STAT5B
Protein: p.Val712Glu
Coding: c.2135T>A
MANE Select: NM_012448
Type: single nucleotide variant
Location: chr17:42202442 (GRCh38)
Gene constraint: LOEUF 0.277 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.90 · 2 PDB

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

Disease context

growth hormone insensitivity with immune dysregulation 1, autosomal recessive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Laron syndrome with immunodeficiency (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Childhood, Infancy, Neonatal

Similar variants

STAT5B c.1906+1G>A Likely pathogenic ★★ same condition
STAT5B p.Ala20Glu Uncertain significance ★★ ⚠ same condition
STAT5B p.Ala20Val Uncertain significance ★★ ⚠ same condition
STAT5B p.Ala213Gly Uncertain significance ★★ ⚠ same condition
STAT5B p.Ala213Ser Uncertain significance ★★ ⚠ same condition
STAT5B p.Ala723Thr Uncertain significance ★★ ⚠ same condition
STAT5B p.Ala785Thr Uncertain significance ★★ ⚠ same condition
STAT5B p.Arg121Leu 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/stat5b-p-val712glu (accessed [today's date]).

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