Is GSPT2 p.Phe404= (c.1212C>T) pathogenic?

GSPT2 p.Phe404= (c.1212C>T) is classified Likely benign in GSPT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-26). Very rare (popmax 0.000224%, nfe).

How common is GSPT2 p.Phe404= (c.1212C>T) in the general population?

GSPT2 p.Phe404= (c.1212C>T) is very rare (popmax 0.000224%, nfe) (gnomAD).

GSPT2 p.Phe404=

c.1212C>T · VCV4950789

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000224%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.28	GERP 0.95, phastCons 0.98
Overall
CADD	9.105	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000224% European (non-Finnish) · 2/893,141 alleles

Filtering AF 3.7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.4e-05%

Overall 0.000165% 2/1,209,244 alleles · very rare exomes 2/1,095,514 · genomes 0/113,730 · joint denominator

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: GSPT2
Protein: p.Phe404=
Coding: c.1212C>T
MANE Select: NM_018094
Type: single nucleotide variant
Location: chrX:51744838 (GRCh38)
Structure: AlphaFold pLDDT 75.18 · 1 PDB
Residue 404: the tr-type g domain

Full GSPT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GSPT2 p.Phe404Val Uncertain significance ★ ⚠ same residue
GSPT2 p.His517Arg Uncertain significance ★★ ⚠ same type
GSPT2 p.Glu141= Benign ★★ same type
GSPT2 p.Pro23Leu Benign ★★ same type
GSPT2 p.Ala314Ser Uncertain significance ★ ⚠ same type
GSPT2 p.Ala35Thr Uncertain significance ★ ⚠ same type
GSPT2 p.Asn53Ile Uncertain significance ★ ⚠ same type
GSPT2 p.Asn53Lys 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/gspt2-p-phe404 (accessed [today's date]).

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