Is STAT2 p.Val623Met (c.1867G>A) pathogenic?

STAT2 p.Val623Met (c.1867G>A) is classified Uncertain significance in STAT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-12). AlphaMissense: likely benign (0.2073); Very rare (popmax 0.0011%, sas); Associated with Inborn genetic diseases.

What condition is associated with STAT2 p.Val623Met (c.1867G>A)?

STAT2 p.Val623Met (c.1867G>A) is associated with Inborn genetic diseases (ClinVar).

How common is STAT2 p.Val623Met (c.1867G>A) in the general population?

STAT2 p.Val623Met (c.1867G>A) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about STAT2 p.Val623Met (c.1867G>A)?

AlphaMissense predicts likely benign (score 0.2073) — an in-silico prediction, not a clinical call.

STAT2 p.Val623Met

c.1867G>A · rs2547244856 · VCV3171110

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2073 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2073	likely benign
REVEL	0.294	indeterminate
SaProt	LLR -11.58	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 0.83, phastCons 0.98
Regional constraint	o/e 0.73	unconstrained · MANE · 13 kb · p 6.2e-18 · regional, not allelic
Overall
CADD	22.5	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 0.0011% South Asian · 1/91,068 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00031% 5/1,614,080 alleles · very rare exomes 5/1,461,808 · genomes 0/152,272 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,068
European (non-Finnish)	0.000339%	295,002

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: STAT2
Protein: p.Val623Met
Coding: c.1867G>A
MANE Select: NM_005419
dbSNP: rs2547244856
Type: single nucleotide variant
Location: chr12:56346619 (GRCh38)
Gene constraint: LOEUF 0.497 · pLI 0.81 (gnomAD)
Structure: AlphaFold pLDDT 78.45 · 6 PDB
Residue 623: the sh2 domain; a β-strand

Full STAT2 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

STAT2 p.Ala219Thr Uncertain significance ★★ ⚠ same condition
STAT2 p.Ala302Thr Uncertain significance ★★ ⚠ same condition
STAT2 p.Arg300Cys Uncertain significance ★★ ⚠ same condition
STAT2 p.Arg409His Uncertain significance ★★ ⚠ same condition
STAT2 p.Arg576Cys Uncertain significance ★★ ⚠ same condition
STAT2 p.Arg646Cys Uncertain significance ★★ ⚠ same condition
STAT2 p.Asn700Ser Uncertain significance ★★ ⚠ same condition
STAT2 p.Asp558Glu 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/stat2-p-val623met (accessed [today's date]).

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