Is STAT6 p.Ala358Val (c.1073C>T) pathogenic?

STAT6 p.Ala358Val (c.1073C>T) is classified Uncertain significance in STAT6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-10). AlphaMissense: likely pathogenic (0.5929); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with STAT6 p.Ala358Val (c.1073C>T)?

STAT6 p.Ala358Val (c.1073C>T) is associated with Inborn genetic diseases (ClinVar).

How common is STAT6 p.Ala358Val (c.1073C>T) in the general population?

STAT6 p.Ala358Val (c.1073C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about STAT6 p.Ala358Val (c.1073C>T)?

AlphaMissense predicts likely pathogenic (score 0.5929) — an in-silico prediction, not a clinical call.

STAT6 p.Ala358Val

c.1073C>T · rs2034166966 · VCV2535703

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5929 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5929	likely pathogenic
REVEL	0.561	indeterminate
SaProt	LLR -10.11	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.32	constrained · MANE · 238 bp · p 1.2e-05 · regional, not allelic
Overall
CADD	27.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00167% Admixed American · 1/59,994 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000372% 6/1,613,996 alleles · very rare exomes 5/1,461,878 · genomes 1/152,118 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,994
European (non-Finnish)	0.000424%	236,005

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.Ala358Val
Coding: c.1073C>T
MANE Select: NM_003153
dbSNP: rs2034166966
Type: single nucleotide variant
Location: chr12:57104742 (GRCh38)
Gene constraint: LOEUF 0.515 · pLI 0.56 (gnomAD)
Structure: AlphaFold pLDDT 77.44 · 7 PDB
Residue 358: a β-strand

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.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
STAT6 p.Arg135Trp 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-ala358val (accessed [today's date]).

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