Is GSPT2 p.Phe507= (c.1521C>T) pathogenic?

GSPT2 p.Phe507= (c.1521C>T) is classified Likely benign in GSPT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-01). Ultra-rare (popmax 0.0195%, amr).

How common is GSPT2 p.Phe507= (c.1521C>T) in the general population?

GSPT2 p.Phe507= (c.1521C>T) is ultra-rare (popmax 0.0195%, amr) (gnomAD).

GSPT2 p.Phe507=

c.1521C>T · rs781793704 · VCV2660573

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0195%, amr)

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 2.2	GERP 0.99, phastCons 1
Overall
CADD	10.65	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0195% Admixed American · 9/46,037 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00752%

Overall 0.00166% 20/1,206,562 alleles · ultra-rare exomes 20/1,092,953 · genomes 0/113,609 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0195%	5,115
Remaining individualsnot grpmax-eligible	0.00211%	47,505
European (non-Finnish)	0.00112%	89,074

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.Phe507=
Coding: c.1521C>T
MANE Select: NM_018094
dbSNP: rs781793704
Type: single nucleotide variant
Location: chrX:51745147 (GRCh38)
Structure: AlphaFold pLDDT 75.18 · 1 PDB

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

Similar variants

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
GSPT2 p.Asn53Ser 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-phe507 (accessed [today's date]).

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