Is STAT3 p.Trp623fs (c.1866_1881del) pathogenic?

STAT3 p.Trp623fs (c.18661881del) is classified Uncertain significance in STAT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-01). No gnomAD frequency available for this variant.

How common is STAT3 p.Trp623fs (c.1866_1881del) in the general population?

STAT3 p.Trp623fs (c.1866_1881del) is no gnomAD frequency available for this variant (gnomAD).

STAT3 p.Trp623fs

c.1866_1881del · rs2509210680 · VCV3251208

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 20 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 1.8, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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: STAT3
Protein: p.Trp623fs
Coding: c.1866_1881del
MANE Select: NM_139276
dbSNP: rs2509210680
Type: Deletion
Location: chr17:42323011 (GRCh38)
Gene constraint: LOEUF 0.109 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.80 · 6 PDB
Residue 623: a β-strand; the sh2 domain

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

Similar variants

STAT3 p.Trp623Leu Likely pathogenic ★ same residue
STAT3 p.Trp623Cys Uncertain significance ★ ⚠ same residue
STAT3 p.Trp623Ter Uncertain significance ★ same residue
STAT3 c.1365+143_1365+146del Benign/Likely benign ★★ same type
STAT3 c.468+58del Benign/Likely benign ★★ same type
STAT3 c.469-34_469-30del Benign/Likely benign ★★ same type
STAT3 c.551-137_551-18del Benign ★★ same type
STAT3 c.1110-2_1115del 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/stat3-p-trp623fs (accessed [today's date]).

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