Is STAT5B p.Ala510Val (c.1529C>T) pathogenic?

STAT5B p.Ala510Val (c.1529C>T) is classified Conflicting classifications of pathogenicity in STAT5B (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-02). AlphaMissense: ambiguous (0.4366); Ultra-rare (popmax 0.025%, amr); Associated with Inborn genetic diseases.

What condition is associated with STAT5B p.Ala510Val (c.1529C>T)?

STAT5B p.Ala510Val (c.1529C>T) is associated with Inborn genetic diseases, growth hormone insensitivity with immune dysregulation 1, autosomal recessive (ClinVar).

How common is STAT5B p.Ala510Val (c.1529C>T) in the general population?

STAT5B p.Ala510Val (c.1529C>T) is ultra-rare (popmax 0.025%, amr) (gnomAD).

What do computational predictors say about STAT5B p.Ala510Val (c.1529C>T)?

AlphaMissense predicts ambiguous (score 0.4366) — an in-silico prediction, not a clinical call.

STAT5B p.Ala510Val

c.1529C>T · rs200200711 · VCV572798

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4366 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.025%, amr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4366	ambiguous
REVEL	0.68	pathogenic-leaning
SaProt	LLR -8.40	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 7,078 bp · p 1.5e-09 · regional, not allelic
Overall
CADD	24.5	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 0.025% Admixed American · 15/59,988 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0124%

Overall 0.0126% 204/1,614,020 alleles · ultra-rare exomes 172/1,461,858 · genomes 32/152,162 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.409%	245
Remaining individualsnot grpmax-eligible	0.0336%	2,975
Admixed Americangrpmax	0.025%	3,999
African / African-American	0.00801%	12,484
European (non-Finnish)	0.00331%	30,257
East Asian	0.00223%	44,898
South Asian	0.0011%	91,078

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala510Val
Coding: c.1529C>T
MANE Select: NM_012448
dbSNP: rs200200711
Type: single nucleotide variant
Location: chr17:42212135 (GRCh38)
Gene constraint: LOEUF 0.277 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.90 · 2 PDB
Residue 510: an α-helix

Full STAT5B 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: growth hormone insensitivity with immune dysregulation 1, autosomal recessive

Similar variants

STAT5B p.Ala510= Likely benign ★ same residue
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

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-ala510val (accessed [today's date]).

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