Is STAT6 p.Ser176Asn (c.527G>A) pathogenic?

STAT6 p.Ser176Asn (c.527G>A) is classified Likely benign in STAT6 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-20). AlphaMissense: likely benign (0.0826); Absent from gnomAD v4.1; Associated with hyper-IgE syndrome 6, autosomal dominant, with recurrent infections.

What condition is associated with STAT6 p.Ser176Asn (c.527G>A)?

STAT6 p.Ser176Asn (c.527G>A) is associated with hyper-IgE syndrome 6, autosomal dominant, with recurrent infections (ClinVar).

How common is STAT6 p.Ser176Asn (c.527G>A) in the general population?

STAT6 p.Ser176Asn (c.527G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about STAT6 p.Ser176Asn (c.527G>A)?

AlphaMissense predicts likely benign (score 0.0826) — an in-silico prediction, not a clinical call.

STAT6 p.Ser176Asn

c.527G>A · VCV4851556

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0826 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hyper-IgE syndrome 6, autosomal dominant, with recurrent infections

Computational evidence

Protein change
AlphaMissense	0.0826	likely benign
REVEL	0.065	moderately benign-leaning
SaProt	LLR -8.46	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 -0.23	GERP -2.8
Regional constraint	o/e 0.78	unconstrained · MANE · 3,517 bp · p 6e-06 · regional, not allelic
Overall
CADD	9.973	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: STAT6
Protein: p.Ser176Asn
Coding: c.527G>A
MANE Select: NM_003153
Type: single nucleotide variant
Location: chr12:57106532 (GRCh38)
Gene constraint: LOEUF 0.515 · pLI 0.56 (gnomAD)
Structure: AlphaFold pLDDT 77.44 · 7 PDB

Full STAT6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hyper-IgE syndrome 6, autosomal dominant, with recurrent infections — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

STAT6 p.Asp419His Likely pathogenic ★ same condition
STAT6 p.Cys762Tyr Uncertain significance ★ ⚠ same condition
STAT6 p.Glu808Gln Uncertain significance ★ ⚠ same condition
STAT6 p.Gly158Ser Uncertain significance ★ ⚠ same condition
STAT6 p.Phe289Tyr Uncertain significance ★ ⚠ same condition
STAT6 p.Asp419Gly Pathogenic same condition
STAT6 p.Asp419Tyr Pathogenic same condition
STAT6 p.Asp519His 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/stat6-p-ser176asn (accessed [today's date]).

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