Is STAT6 p.Val438Met (c.1312G>A) pathogenic?

STAT6 p.Val438Met (c.1312G>A) is classified Uncertain significance in STAT6 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-01). AlphaMissense: likely benign (0.1657); Very rare (popmax 0.00769%, sas); Associated with Inborn genetic diseases.

What condition is associated with STAT6 p.Val438Met (c.1312G>A)?

STAT6 p.Val438Met (c.1312G>A) is associated with Inborn genetic diseases (ClinVar).

How common is STAT6 p.Val438Met (c.1312G>A) in the general population?

STAT6 p.Val438Met (c.1312G>A) is very rare (popmax 0.00769%, sas) (gnomAD).

What do computational predictors say about STAT6 p.Val438Met (c.1312G>A)?

AlphaMissense predicts likely benign (score 0.1657) — an in-silico prediction, not a clinical call.

STAT6 p.Val438Met

c.1312G>A · rs533111994 · VCV2323907

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1657 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00769%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1657	likely benign
REVEL	0.56	indeterminate
SaProt	LLR -8.51	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP 2.5, phastCons 0.92
Regional constraint	o/e 0.63	unconstrained · MANE · 5,635 bp · p 1.9e-12 · regional, not allelic
Overall
CADD	20.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00769% South Asian · 7/91,032 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00321%

Overall 0.00403% 65/1,613,470 alleles · very rare exomes 60/1,461,224 · genomes 5/152,246 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00769%	13,005
European (non-Finnish)	0.00458%	21,851
East Asian	0.00446%	22,435
Remaining individualsnot grpmax-eligible	0.0032%	31,224

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.Val438Met
Coding: c.1312G>A
MANE Select: NM_003153
dbSNP: rs533111994
Type: single nucleotide variant
Location: chr12:57102490 (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-val438met (accessed [today's date]).

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