Is STAT1 p.Phe172Leu (c.514T>C) pathogenic?

STAT1 p.Phe172Leu (c.514T>C) is classified Pathogenic in STAT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-05-04). AlphaMissense: likely pathogenic (0.9981); Absent from gnomAD v4.1; Associated with STAT1-related disorder.

What condition is associated with STAT1 p.Phe172Leu (c.514T>C)?

STAT1 p.Phe172Leu (c.514T>C) is associated with STAT1-related disorder, immunodeficiency 31B (ClinVar).

How common is STAT1 p.Phe172Leu (c.514T>C) in the general population?

STAT1 p.Phe172Leu (c.514T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about STAT1 p.Phe172Leu (c.514T>C)?

AlphaMissense predicts likely pathogenic (score 0.9981) — an in-silico prediction, not a clinical call.

STAT1 p.Phe172Leu

c.514T>C · rs2125075036 · VCV1686231

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9981 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

STAT1-related disorder

Computational evidence

Protein change
AlphaMissense	0.9981	likely pathogenic ✓ concordant with ClinVar · top 3% in STAT1
REVEL	0.72	pathogenic-leaning
SaProt	LLR -4.74	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.42	unconstrained · MANE · 5,939 bp · p 3.1e-13 · regional, not allelic
Overall
CADD	28.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: STAT1
Protein: p.Phe172Leu
Coding: c.514T>C
MANE Select: NM_007315
dbSNP: rs2125075036
Type: single nucleotide variant
Location: chr2:190999653 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 87.78 · 10 PDB
Residue 172: an α-helix

Full STAT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

STAT1-related disorder

Also linked: immunodeficiency 31B

Similar variants

STAT1 p.Ala267Val Pathogenic ★★ ⚠ same condition
STAT1 p.Arg274Gln Pathogenic ★★ ⚠ same condition
STAT1 p.Arg274Gly Pathogenic/Likely pathogenic ★★ same condition
STAT1 p.Arg274Trp Pathogenic ★★ same condition
STAT1 p.Asp171Asn Likely pathogenic ★★ ⚠ same condition
STAT1 p.Asp292Glu Likely pathogenic ★★ ⚠ same condition
STAT1 p.Cys324Arg Likely pathogenic ★★ same condition
STAT1 p.Gln271Pro Pathogenic/Likely pathogenic ★★ ⚠ 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/stat1-p-phe172leu (accessed [today's date]).

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