Is STAT6 p.Asp604Asn (c.1810G>A) pathogenic?

STAT6 p.Asp604Asn (c.1810G>A) is classified Uncertain significance in STAT6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-09). AlphaMissense: likely pathogenic (0.9436); Very rare (popmax 0.00661%, nfe); Associated with Inborn genetic diseases.

What condition is associated with STAT6 p.Asp604Asn (c.1810G>A)?

STAT6 p.Asp604Asn (c.1810G>A) is associated with Inborn genetic diseases (ClinVar).

How common is STAT6 p.Asp604Asn (c.1810G>A) in the general population?

STAT6 p.Asp604Asn (c.1810G>A) is very rare (popmax 0.00661%, nfe) (gnomAD).

What do computational predictors say about STAT6 p.Asp604Asn (c.1810G>A)?

AlphaMissense predicts likely pathogenic (score 0.9436) — an in-silico prediction, not a clinical call.

STAT6 p.Asp604Asn

c.1810G>A · rs373679457 · VCV2205744

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9436 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00661%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9436	likely pathogenic
REVEL	0.806	moderately pathogenic-leaning
SaProt	LLR -9.21	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 7.7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 5,635 bp · p 1.9e-12 · regional, not allelic
Overall
CADD	28.5	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

Grpmax group 0.00661% European (non-Finnish) · 78/1,180,006 alleles

Filtering AF 0.00538% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00498%

Overall 0.00731% 118/1,613,992 alleles · very rare exomes 82/1,461,874 · genomes 36/152,118 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	3.51%	29
European (non-Finnish)grpmax	0.00661%	15,128
Finnishnot grpmax-eligible	0.00625%	16,009
Admixed American	0.00333%	30,001
Remaining individualsnot grpmax-eligible	0.0032%	31,242

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: STAT6
Protein: p.Asp604Asn
Coding: c.1810G>A
MANE Select: NM_003153
dbSNP: rs373679457
Type: single nucleotide variant
Location: chr12:57099375 (GRCh38)
Gene constraint: LOEUF 0.515 · pLI 0.56 (gnomAD)
Structure: AlphaFold pLDDT 77.44 · 7 PDB
Residue 604: the sh2 domain; an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

STAT6 p.Ala109Val Uncertain significance ★ ⚠ same condition
STAT6 p.Ala245Val Uncertain significance ★ ⚠ same condition
STAT6 p.Ala304Asp Uncertain significance ★ ⚠ same condition
STAT6 p.Ala358Val Uncertain significance ★ ⚠ same condition
STAT6 p.Ala385Thr Uncertain significance ★ same condition
STAT6 p.Ala753Thr Uncertain significance ★ ⚠ same condition
STAT6 p.Ala779Val Uncertain significance ★ ⚠ same condition
STAT6 p.Arg115Cys Uncertain significance ★ ⚠ 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-asp604asn (accessed [today's date]).

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