Is GFI1 p.Pro23= (c.69A>G) pathogenic?

GFI1 p.Pro23= (c.69A>G) is classified Likely benign in GFI1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-18). Very rare (popmax 0.00267%, afr); Associated with neutropenia, severe congenital, 2, autosomal dominant.

What condition is associated with GFI1 p.Pro23= (c.69A>G)?

GFI1 p.Pro23= (c.69A>G) is associated with neutropenia, severe congenital, 2, autosomal dominant (ClinVar).

How common is GFI1 p.Pro23= (c.69A>G) in the general population?

GFI1 p.Pro23= (c.69A>G) is very rare (popmax 0.00267%, afr) (gnomAD).

GFI1 p.Pro23=

Q: How is Autosomal dominant severe congenital neutropenia inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.69A>G · rs369812626 · VCV1145178

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

neutropenia, severe congenital, 2, autosomal dominant

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 -1.5	GERP -3.3
Overall
CADD	9.286	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,928 alleles

Filtering AF 0.000543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000429%

Overall 0.000868% 14/1,613,452 alleles · very rare exomes 11/1,461,244 · genomes 3/152,208 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,464
European (non-Finnish)	0.00102%	98,295

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.Pro23=
Coding: c.69A>G
MANE Select: NM_005263
dbSNP: rs369812626
Type: single nucleotide variant
Location: chr1:92483419 (GRCh38)
Gene constraint: LOEUF 0.715 · pLI 0.05 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 58.33
Residue 23: the 'disordered' region

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

Disease context

neutropenia, severe congenital, 2, autosomal dominant — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal dominant severe congenital neutropenia (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy, Neonatal
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

GFI1 p.Asn382Ser Pathogenic ★★ ⚠ same condition
GFI1 p.Ala128Glu Uncertain significance ★★ ⚠ same condition
GFI1 p.Ala128Gly Uncertain significance ★★ ⚠ same condition
GFI1 p.Ala144Gly Uncertain significance ★★ ⚠ same condition
GFI1 p.Ala158Ser Uncertain significance ★★ ⚠ same condition
GFI1 p.Ala165Asp Uncertain significance ★★ ⚠ same condition
GFI1 p.Ala174Val Uncertain significance ★★ ⚠ same condition
GFI1 p.Ala179Thr 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/gfi1-p-pro23 (accessed [today's date]).

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