Is GPI p.Phe293= (c.879C>T) pathogenic?

GPI p.Phe293= (c.879C>T) is classified Likely benign in GPI (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-29). Ultra-rare (popmax 0.0121%, sas); Associated with Inborn genetic diseases.

What condition is associated with GPI p.Phe293= (c.879C>T)?

GPI p.Phe293= (c.879C>T) is associated with Inborn genetic diseases (ClinVar).

How common is GPI p.Phe293= (c.879C>T) in the general population?

GPI p.Phe293= (c.879C>T) is ultra-rare (popmax 0.0121%, sas) (gnomAD).

GPI p.Phe293=

c.879C>T · VCV4031264

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0121%, sas)

Conditions

Inborn genetic diseases

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 -11	GERP -4.3
Overall
CADD	7.283	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0121% South Asian · 11/91,036 alleles

Filtering AF 0.00677% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00522%

Overall 0.00484% 78/1,613,134 alleles · ultra-rare exomes 73/1,461,314 · genomes 5/151,820 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0121%	8,276
European (non-Finnish)	0.00534%	18,730
Remaining individualsnot grpmax-eligible	0.0032%	31,236
African / African-American	0.00267%	37,406

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: GPI
Protein: p.Phe293=
Coding: c.879C>T
MANE Select: NM_000175
Type: single nucleotide variant
Location: chr19:34393741 (GRCh38)
Structure: AlphaFold pLDDT 93.81 · 1 PDB

Full GPI 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

GPI p.Ala350Thr Uncertain significance ★★ ⚠ same condition
GPI p.Ala540Thr Uncertain significance ★★ ⚠ same condition
GPI p.Arg135His Uncertain significance ★★ ⚠ same condition
GPI p.Arg553Cys Uncertain significance ★★ same condition
GPI p.Arg556Ser Uncertain significance ★★ ⚠ same condition
GPI p.Arg6Trp Uncertain significance ★★ ⚠ same condition
GPI p.Asp31His Uncertain significance ★★ ⚠ same condition
GPI p.Ile477Met 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/gpi-p-phe293 (accessed [today's date]).

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