Is GFI1 p.Phe89= (c.267C>T) pathogenic?

GFI1 p.Phe89= (c.267C>T) is classified Likely benign in GFI1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-26). Very rare (popmax 0.0011%, sas).

How common is GFI1 p.Phe89= (c.267C>T) in the general population?

GFI1 p.Phe89= (c.267C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

GFI1 p.Phe89=

c.267C>T · VCV4671560

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

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 1.3	GERP -3.6, phastCons 1
Overall
CADD	11.82	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,090 alleles

Overall 6.2e-05% 1/1,614,144 alleles · very rare exomes 1/1,461,780 · genomes 0/152,364 · 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: GFI1
Protein: p.Phe89=
Coding: c.267C>T
MANE Select: NM_005263
Type: single nucleotide variant
Location: chr1:92482895 (GRCh38)
Gene constraint: LOEUF 0.715 · pLI 0.05 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 58.33
Residue 89: the 'disordered' region

Full GFI1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GFI1 p.Phe89Leu Uncertain significance ★ ⚠ same residue
GFI1 p.Phe89fs Uncertain significance ★ same residue
GFI1 p.Asn382Ser Pathogenic ★★ ⚠ same type
GFI1 p.Ala128Glu Uncertain significance ★★ ⚠ same type
GFI1 p.Ala128Gly Uncertain significance ★★ ⚠ same type
GFI1 p.Ala144Gly Uncertain significance ★★ ⚠ same type
GFI1 p.Ala158Ser Uncertain significance ★★ ⚠ same type
GFI1 p.Ala165Asp 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/gfi1-p-phe89 (accessed [today's date]).

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