Is STAT3 p.Pro330Ser (c.988C>T) pathogenic?

STAT3 p.Pro330Ser (c.988C>T) is classified Pathogenic in STAT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-18). AlphaMissense: likely pathogenic (0.9779); Absent from gnomAD v4.1.

How common is STAT3 p.Pro330Ser (c.988C>T) in the general population?

STAT3 p.Pro330Ser (c.988C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about STAT3 p.Pro330Ser (c.988C>T)?

AlphaMissense predicts likely pathogenic (score 0.9779) — an in-silico prediction, not a clinical call.

STAT3 p.Pro330Ser

c.988C>T · rs2144828091 · VCV1800571

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9779 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9779	likely pathogenic ✓ concordant with ClinVar
REVEL	0.856	moderately pathogenic-leaning
SaProt	LLR -11.99	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.39	unconstrained · MANE · 25 kb · p 2.4e-61 · regional, not allelic
Overall
CADD	29.8	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.Pro330Ser
Coding: c.988C>T
MANE Select: NM_139276
dbSNP: rs2144828091
Type: single nucleotide variant
Location: chr17:42333734 (GRCh38)
Gene constraint: LOEUF 0.109 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.80 · 6 PDB
Residue 330: a UniProt-annotated variant site (in admio1; increases transcriptional activity; increases binding to isl1 promoter region; decreases glucose stimulated insulin secretion)

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

Similar variants

STAT3 p.Pro330= Likely benign ★ same residue
STAT3 p.Arg152Trp Pathogenic ★★ ⚠ same type
STAT3 p.Arg278Cys Likely pathogenic ★★ same type
STAT3 p.Arg335Trp Pathogenic/Likely pathogenic ★★ same type
STAT3 p.Arg382Gln Pathogenic ★★ same type
STAT3 p.Arg382Trp Pathogenic ★★ same type
STAT3 p.Arg423Gln Pathogenic ★★ ⚠ same type
STAT3 p.Asn466Ser Pathogenic ★★ ⚠ 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/stat3-p-pro330ser (accessed [today's date]).

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