Is STAT3 p.Pro715Gln (c.2144C>A) pathogenic?

STAT3 p.Pro715Gln (c.2144C>A) is classified Likely pathogenic in STAT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-13). AlphaMissense: likely pathogenic (0.701); Absent from gnomAD v4.1; Associated with STAT3-related disorder.

What condition is associated with STAT3 p.Pro715Gln (c.2144C>A)?

STAT3 p.Pro715Gln (c.2144C>A) is associated with STAT3-related disorder (ClinVar).

How common is STAT3 p.Pro715Gln (c.2144C>A) in the general population?

STAT3 p.Pro715Gln (c.2144C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about STAT3 p.Pro715Gln (c.2144C>A)?

AlphaMissense predicts likely pathogenic (score 0.701) — an in-silico prediction, not a clinical call.

STAT3 p.Pro715Gln

c.2144C>A · VCV4935207

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.701 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

STAT3-related disorder

Computational evidence

Protein change
AlphaMissense	0.701	likely pathogenic ✓ concordant with ClinVar
REVEL	0.701	pathogenic-leaning
SaProt	LLR -7.93	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 0.05	constrained · MANE · 327 bp · p 1.3e-05 · regional, not allelic
Overall
CADD	33.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: STAT3
Protein: p.Pro715Gln
Coding: c.2144C>A
MANE Select: NM_139276
Type: single nucleotide variant
Location: chr17:42317182 (GRCh38)
Gene constraint: LOEUF 0.109 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.80 · 6 PDB
Residue 715: a UniProt-annotated variant site (in admio1; likely pathogenic)

Full STAT3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

STAT3-related disorder

Similar variants

STAT3 p.Pro715Leu Pathogenic/Likely pathogenic ★★ ⚠ same residue
STAT3 p.Arg152Trp Pathogenic ★★ ⚠ same condition
STAT3 p.Gly421Arg Pathogenic/Likely pathogenic ★★ ⚠ same condition
STAT3 p.His332Tyr Pathogenic/Likely pathogenic ★★ ⚠ same condition
STAT3 p.Thr716Met Pathogenic ★★ ⚠ same condition
STAT3 p.Cys718Tyr Uncertain significance ★★ ⚠ same condition
STAT3 c.551-1G>A Likely pathogenic ★ same condition
STAT3 p.Asn466Asp Likely pathogenic ★ 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/stat3-p-pro715gln (accessed [today's date]).

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