Is STAT5A p.Val209Ala (c.626T>C) pathogenic?

STAT5A p.Val209Ala (c.626T>C) is classified Benign in STAT5A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.0776); Common (popmax 7.18%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about STAT5A p.Val209Ala (c.626T>C)?

AlphaMissense predicts likely benign (score 0.0776) — an in-silico prediction, not a clinical call.

STAT5A p.Val209Ala

Q: How common is STAT5A p.Val209Ala (c.626T>C) in the general population?

STAT5A p.Val209Ala (c.626T>C) is common (popmax 7.18%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.626T>C · rs2230123 · VCV785569

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0776 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 7.18%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0776	likely benign
REVEL	0.076	moderately benign-leaning
SaProt	LLR -4.45	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 2.8	GERP 0.78, phastCons 1
Regional constraint	o/e 0.32	constrained · MANE · 897 bp · p 1.6e-11 · regional, not allelic
Overall
CADD	15.39	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 7.18% African / African-American · 5,362/74,708 alleles

Filtering AF 7.02% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.95%

Overall 0.419% 6,766/1,612,930 alleles · common exomes 3,731/1,461,442 · genomes 3,035/151,488 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.18%	14
Middle Eastern	1.01%	99
Admixed American	0.594%	168
Remaining individualsnot grpmax-eligible	0.568%	176
South Asian	0.173%	580
European (non-Finnish)	0.0395%	2,532
East Asian	0.0245%	4,075

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: STAT5A
Protein: p.Val209Ala
Coding: c.626T>C
MANE Select: NM_001288718
dbSNP: rs2230123
Type: single nucleotide variant
Location: chr17:42299826 (GRCh38)
Gene constraint: LOEUF 0.364 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.78 · 5 PDB
Residue 209: an α-helix

Full STAT5A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

STAT5A c.2063-4A>G Benign ★★ same type
STAT5A p.Asp743= Benign ★★ same type
STAT5A p.Leu746= Benign ★★ same type
STAT5A p.Ala213Val Uncertain significance ★ ⚠ same type
STAT5A p.Ala318Thr Uncertain significance ★ ⚠ same type
STAT5A p.Ala45Ser Uncertain significance ★ ⚠ same type
STAT5A p.Ala510Thr Uncertain significance ★ ⚠ same type
STAT5A p.Ala510Val Uncertain significance ★ ⚠ same type

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/stat5a-p-val209ala (accessed [today's date]).

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