Is INF2 p.Pro1023= (c.3069C>T) pathogenic?

INF2 p.Pro1023= (c.3069C>T) is classified Benign/Likely benign in INF2 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-06-01). Low-frequency (popmax 1.12%, mid); Associated with focal segmental glomerulosclerosis 5.

What condition is associated with INF2 p.Pro1023= (c.3069C>T)?

INF2 p.Pro1023= (c.3069C>T) is associated with focal segmental glomerulosclerosis 5, Charcot-Marie-Tooth disease dominant intermediate E, focal segmental glomerulosclerosis (ClinVar).

How common is INF2 p.Pro1023= (c.3069C>T) in the general population?

INF2 p.Pro1023= (c.3069C>T) is low-frequency (popmax 1.12%, mid) (gnomAD).

INF2 p.Pro1023=

c.3069C>T · rs75382114 · VCV261614

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.12%, mid)

Conditions

focal segmental glomerulosclerosis 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -6	GERP -0.27
Overall
CADD	2.231	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.12% Middle Eastern · 66/5,918 alleles

Filtering AF 0.899% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.821%

Overall 0.606% 9,472/1,563,498 alleles · low-frequency exomes 8,754/1,411,208 · genomes 718/152,290 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	1.12%	90
European (non-Finnish)	0.688%	145
Remaining individualsnot grpmax-eligible	0.659%	152
Admixed American	0.658%	152
South Asian	0.389%	257
Finnishnot grpmax-eligible	0.339%	295
Ashkenazi Jewishnot grpmax-eligible	0.238%	420
African / African-American	0.128%	779
East Asian	0.014%	7,126

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: INF2
Protein: p.Pro1023=
Coding: c.3069C>T
MANE Select: NM_022489
dbSNP: rs75382114
Type: single nucleotide variant
Location: chr14:104714231 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.33 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.34 · 10 PDB
Residue 1023: the 'disordered' region

Full INF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

focal segmental glomerulosclerosis 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Charcot-Marie-Tooth disease dominant intermediate E focal segmental glomerulosclerosis

Similar variants

INF2 p.Arg177Cys Pathogenic/Likely pathogenic ★★ same condition
INF2 p.Arg214Cys Pathogenic/Likely pathogenic ★★ same condition
INF2 p.Arg214His Pathogenic/Likely pathogenic ★★ same condition
INF2 p.Arg218Gln Pathogenic/Likely pathogenic ★★ same condition
INF2 p.Arg218Trp Pathogenic/Likely pathogenic ★★ same condition
INF2 p.Arg91Gly Pathogenic/Likely pathogenic ★★ same condition
INF2 p.Asn202Asp Likely pathogenic ★★ same condition
INF2 p.Glu184Lys Pathogenic ★★ 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/inf2-p-pro1023 (accessed [today's date]).

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