Is STAT6 p.Val714Met (c.2140G>A) pathogenic?

STAT6 p.Val714Met (c.2140G>A) is classified Conflicting classifications of pathogenicity in STAT6 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-06-13). AlphaMissense: likely benign (0.0754); Low-frequency (popmax 1%, afr); Associated with Inborn genetic diseases.

What condition is associated with STAT6 p.Val714Met (c.2140G>A)?

STAT6 p.Val714Met (c.2140G>A) is associated with Inborn genetic diseases (ClinVar).

How common is STAT6 p.Val714Met (c.2140G>A) in the general population?

STAT6 p.Val714Met (c.2140G>A) is low-frequency (popmax 1%, afr) (gnomAD).

What do computational predictors say about STAT6 p.Val714Met (c.2140G>A)?

AlphaMissense predicts likely benign (score 0.0754) — an in-silico prediction, not a clinical call.

STAT6 p.Val714Met

c.2140G>A · rs147655222 · VCV733917

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0754 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0754	likely benign
REVEL	0.149	moderately benign-leaning
SaProt	LLR -6.24	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 0.56	GERP -1.2, phastCons 0.37
Regional constraint	o/e 0.95	unconstrained · MANE · 2,310 bp · p 0.49 · regional, not allelic
Overall
CADD	10.49	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 1% African / African-American · 752/75,026 alleles

Filtering AF 0.943% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.919%

Overall 0.0504% 813/1,614,166 alleles · low-frequency exomes 406/1,461,868 · genomes 407/152,298 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1%	100
Remaining individualsnot grpmax-eligible	0.04%	2,500
Middle Eastern	0.033%	3,031
Admixed American	0.0267%	3,752
European (non-Finnish)	0.00153%	65,558

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.Val714Met
Coding: c.2140G>A
MANE Select: NM_003153
dbSNP: rs147655222
Type: single nucleotide variant
Location: chr12:57098524 (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

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-val714met (accessed [today's date]).

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