Is STAT4 p.Ala46Ser (c.136G>T) pathogenic?

STAT4 p.Ala46Ser (c.136G>T) is classified Uncertain significance in STAT4 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-24). AlphaMissense: likely benign (0.3285); No allele count reported in gnomAD v4.1 (AN 1,540,924).

How common is STAT4 p.Ala46Ser (c.136G>T) in the general population?

STAT4 p.Ala46Ser (c.136G>T) is no allele count reported in gnomAD v4.1 (AN 1,540,924) (gnomAD).

What do computational predictors say about STAT4 p.Ala46Ser (c.136G>T)?

AlphaMissense predicts likely benign (score 0.3285) — an in-silico prediction, not a clinical call.

STAT4 p.Ala46Ser

c.136G>T · rs2471010207 · VCV2059104

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3285 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,540,924)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3285	likely benign
REVEL	0.354	indeterminate
SaProt	LLR -7.39	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.8, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 114 kb · p 8.5e-09 · regional, not allelic
Overall
CADD	26.2	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

No allele count reported in gnomAD v4.1 (AN 1,540,924). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: STAT4
Protein: p.Ala46Ser
Coding: c.136G>T
MANE Select: NM_003151
dbSNP: rs2471010207
Type: single nucleotide variant
Location: chr2:191146750 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI 0.93 (gnomAD)
Structure: AlphaFold pLDDT 86.87

Full STAT4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

STAT4 p.Ala46Val Uncertain significance ★ ⚠ same residue
STAT4 p.Ala245Thr Uncertain significance ★★ ⚠ same type
STAT4 p.Arg241Gln Uncertain significance ★★ ⚠ same type
STAT4 p.Arg70Leu Uncertain significance ★★ ⚠ same type
STAT4 p.Arg87Lys Uncertain significance ★★ ⚠ same type
STAT4 p.Asp513Val Uncertain significance ★★ ⚠ same type
STAT4 p.Cys323Arg Uncertain significance ★★ ⚠ same type
STAT4 p.Gln243Lys 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/stat4-p-ala46ser (accessed [today's date]).

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