Is STAT6 p.Ser564= (c.1692C>T) pathogenic?

STAT6 p.Ser564= (c.1692C>T) is classified Benign/Likely benign in STAT6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-01). Rare (popmax 0.829%, eas).

How common is STAT6 p.Ser564= (c.1692C>T) in the general population?

STAT6 p.Ser564= (c.1692C>T) is rare (popmax 0.829%, eas) (gnomAD).

STAT6 p.Ser564=

c.1692C>T · rs35182390 · VCV719355

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.829%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.38 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.9	GERP -5
Overall
CADD	8.311	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.829% East Asian · 372/44,894 alleles

Filtering AF 0.759% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.732%

Overall 0.454% 7,327/1,614,198 alleles · rare exomes 6,666/1,461,852 · genomes 661/152,346 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	2.17%	46
East Asiangrpmax	0.829%	121
Amishnot grpmax-eligible	0.548%	182
Middle Eastern	0.429%	233
European (non-Finnish)	0.418%	239
Remaining individualsnot grpmax-eligible	0.325%	308
Admixed American	0.245%	408
South Asian	0.237%	422
African / African-American	0.052%	1,924

Finnish 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.Ser564=
Coding: c.1692C>T
MANE Select: NM_003153
dbSNP: rs35182390
Type: single nucleotide variant
Location: chr12:57099819 (GRCh38)
Gene constraint: LOEUF 0.515 · pLI 0.56 (gnomAD)
Structure: AlphaFold pLDDT 77.44 · 7 PDB
Residue 564: the sh2 domain

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

Similar variants

STAT6 c.1001+10G>A Benign ★★ same type
STAT6 c.1213-6C>T Benign ★★ same type
STAT6 c.1744+9A>C Likely benign ★★ same type
STAT6 p.Val269Ile Benign ★★ same type
STAT6 p.Asp419His Likely pathogenic ★ same type
STAT6 p.Ala109Val Uncertain significance ★ ⚠ same type
STAT6 p.Ala245Val Uncertain significance ★ ⚠ same type
STAT6 p.Ala304Asp 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/stat6-p-ser564 (accessed [today's date]).

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