Is STAT5A p.Asn264Ser (c.791A>G) pathogenic?

STAT5A p.Asn264Ser (c.791A>G) is classified Uncertain significance in STAT5A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-21). AlphaMissense: likely pathogenic (0.7295); No allele count reported in gnomAD v4.1 (AN 1,481,262).

How common is STAT5A p.Asn264Ser (c.791A>G) in the general population?

STAT5A p.Asn264Ser (c.791A>G) is no allele count reported in gnomAD v4.1 (AN 1,481,262) (gnomAD).

What do computational predictors say about STAT5A p.Asn264Ser (c.791A>G)?

AlphaMissense predicts likely pathogenic (score 0.7295) — an in-silico prediction, not a clinical call.

STAT5A p.Asn264Ser

c.791A>G · VCV3963116

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7295 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,481,262)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7295	likely pathogenic
REVEL	0.243	benign-leaning
SaProt	LLR -5.67	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 8.1	GERP 1.8, phastCons 1
Regional constraint	o/e 0.32	constrained · MANE · 897 bp · p 1.6e-11 · regional, not allelic
Overall
CADD	22.6	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

No allele count reported in gnomAD v4.1 (AN 1,481,262). 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: STAT5A
Protein: p.Asn264Ser
Coding: c.791A>G
MANE Select: NM_001288718
Type: single nucleotide variant
Location: chr17:42300239 (GRCh38)
Gene constraint: LOEUF 0.364 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.78 · 5 PDB
Residue 264: a turn

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.Val209Ala 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

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-asn264ser (accessed [today's date]).

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