Is STAT6 p.Val269Ile (c.805G>A) pathogenic?

STAT6 p.Val269Ile (c.805G>A) is classified Benign in STAT6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-08-07). AlphaMissense: likely benign (0.1211); Low-frequency (popmax 2.93%, amr).

How common is STAT6 p.Val269Ile (c.805G>A) in the general population?

STAT6 p.Val269Ile (c.805G>A) is low-frequency (popmax 2.93%, amr) (gnomAD).

What do computational predictors say about STAT6 p.Val269Ile (c.805G>A)?

AlphaMissense predicts likely benign (score 0.1211) — an in-silico prediction, not a clinical call.

STAT6 p.Val269Ile

c.805G>A · rs118014438 · VCV778987

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1211 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.93%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1211	likely benign
REVEL	0.058	moderately benign-leaning
SaProt	LLR -7.91	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4	GERP 0.018, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 3,517 bp · p 6e-06 · regional, not allelic
Overall
CADD	18.45	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 2.93% Admixed American · 1,756/60,002 alleles

Filtering AF 2.81% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.77%

Overall 0.197% 3,176/1,614,006 alleles · low-frequency exomes 2,500/1,461,756 · genomes 676/152,250 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	2.93%	34
East Asian	2.32%	43
Remaining individualsnot grpmax-eligible	0.216%	463
South Asian	0.131%	765
African / African-American	0.06%	1,667
Middle Eastern	0.0165%	6,060
European (non-Finnish)	0.0067%	14,936

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.Val269Ile
Coding: c.805G>A
MANE Select: NM_003153
dbSNP: rs118014438
Type: single nucleotide variant
Location: chr12:57105475 (GRCh38)
Gene constraint: LOEUF 0.515 · pLI 0.56 (gnomAD)
Structure: AlphaFold pLDDT 77.44 · 7 PDB
Residue 269: an α-helix

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.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-val269ile (accessed [today's date]).

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