Is STAT6 p.Ser45= (c.135C>T) pathogenic?

STAT6 p.Ser45= (c.135C>T) is classified Likely benign in STAT6 (ClinVar, Single submitter, 3 submitters; last evaluated 2018-03-30). Ultra-rare (popmax 0.0698%, nfe).

How common is STAT6 p.Ser45= (c.135C>T) in the general population?

STAT6 p.Ser45= (c.135C>T) is ultra-rare (popmax 0.0698%, nfe) (gnomAD).

STAT6 p.Ser45=

c.135C>T · rs141476151 · VCV727949

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0698%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.75	GERP -3.9, phastCons 0.014
Overall
CADD	0.131	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0698% European (non-Finnish) · 824/1,180,040 alleles

Filtering AF 0.0658% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0642%

Overall 0.0529% 853/1,613,998 alleles · ultra-rare exomes 816/1,461,826 · genomes 37/152,172 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0698%	1,432
Remaining individualsnot grpmax-eligible	0.0288%	3,471
African / African-American	0.00934%	10,703
Admixed American	0.005%	20,001
Finnishnot grpmax-eligible	0.00156%	63,972

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.Ser45=
Coding: c.135C>T
MANE Select: NM_003153
dbSNP: rs141476151
Type: single nucleotide variant
Location: chr12:57107725 (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

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.Ser564= Benign/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

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-ser45 (accessed [today's date]).

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