Is INF2 p.Phe767= (c.2301C>T) pathogenic?

INF2 p.Phe767= (c.2301C>T) is classified Likely benign in INF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-25). Very rare (popmax 0.007%, amr); Associated with focal segmental glomerulosclerosis 5.

What condition is associated with INF2 p.Phe767= (c.2301C>T)?

INF2 p.Phe767= (c.2301C>T) is associated with focal segmental glomerulosclerosis 5, Charcot-Marie-Tooth disease dominant intermediate E (ClinVar).

How common is INF2 p.Phe767= (c.2301C>T) in the general population?

INF2 p.Phe767= (c.2301C>T) is very rare (popmax 0.007%, amr) (gnomAD).

INF2 p.Phe767=

c.2301C>T · rs900191744 · VCV1590714

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.007%, amr)

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 0.045	GERP 0.17, phastCons 0.88
Overall
CADD	10.41	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.007% Admixed American · 4/57,180 alleles

Filtering AF 0.00233% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0014%

Overall 0.000314% 5/1,591,708 alleles · very rare exomes 4/1,460,112 · genomes 1/131,596 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.007%	14,295
European (non-Finnish)	8.52e-05%	1,174,222

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.Phe767=
Coding: c.2301C>T
MANE Select: NM_022489
dbSNP: rs900191744
Type: single nucleotide variant
Location: chr14:104710998 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.33 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.34 · 10 PDB
Residue 767: the fh2 domain; an α-helix

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

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-phe767 (accessed [today's date]).

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