Is STAT5B p.Ala130Val (c.389C>T) pathogenic?

STAT5B p.Ala130Val (c.389C>T) is classified Likely benign in STAT5B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-29). AlphaMissense: likely benign (0.062); Rare (popmax 0.882%, eas); Associated with growth hormone insensitivity with immune dysregulation 1, autosomal recessive.

What condition is associated with STAT5B p.Ala130Val (c.389C>T)?

STAT5B p.Ala130Val (c.389C>T) is associated with growth hormone insensitivity with immune dysregulation 1, autosomal recessive (ClinVar).

How common is STAT5B p.Ala130Val (c.389C>T) in the general population?

STAT5B p.Ala130Val (c.389C>T) is rare (popmax 0.882%, eas) (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.Ala130Val (c.389C>T)?

AlphaMissense predicts likely benign (score 0.062) — an in-silico prediction, not a clinical call.

STAT5B p.Ala130Val

c.389C>T · rs2277619 · VCV731870

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.062 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.882%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

growth hormone insensitivity with immune dysregulation 1, autosomal recessive

Computational evidence

Protein change
AlphaMissense	0.062	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	LLR -6.96	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 2.4	GERP -0.27, phastCons 0.041
Regional constraint	o/e 1.09	unconstrained · MANE · 1,340 bp · p 0.55 · regional, not allelic
Overall
CADD	16.55	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.882% East Asian · 396/44,880 alleles

Filtering AF 0.811% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.782%

Overall 0.025% 403/1,614,154 alleles · rare exomes 379/1,461,878 · genomes 24/152,276 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.882%	113
Remaining individualsnot grpmax-eligible	0.008%	12,502
Admixed American	0.00167%	60,016
European (non-Finnish)	8.47e-05%	1,180,020

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: STAT5B
Protein: p.Ala130Val
Coding: c.389C>T
MANE Select: NM_012448
dbSNP: rs2277619
Type: single nucleotide variant
Location: chr17:42223543 (GRCh38)
Gene constraint: LOEUF 0.277 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.90 · 2 PDB
Residue 130: a UniProt-annotated variant site (in)

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-ala130val (accessed [today's date]).

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