Is INF2 p.Arg993= (c.2979C>T) pathogenic?

INF2 p.Arg993= (c.2979C>T) is classified Likely benign in INF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-27). Very rare (popmax 0.000933%, nfe); Associated with focal segmental glomerulosclerosis 5.

What condition is associated with INF2 p.Arg993= (c.2979C>T)?

INF2 p.Arg993= (c.2979C>T) is associated with focal segmental glomerulosclerosis 5, Charcot-Marie-Tooth disease dominant intermediate E (ClinVar).

How common is INF2 p.Arg993= (c.2979C>T) in the general population?

INF2 p.Arg993= (c.2979C>T) is very rare (popmax 0.000933%, nfe) (gnomAD).

INF2 p.Arg993=

c.2979C>T · rs372735722 · VCV1086726

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000933%, nfe)

Conditions

focal segmental glomerulosclerosis 5

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 -1.7	GERP -4.7
Overall
CADD	3.399	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000933% European (non-Finnish) · 11/1,179,526 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000683% 11/1,611,630 alleles · very rare exomes 8/1,459,500 · genomes 3/152,130 · 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: INF2
Protein: p.Arg993=
Coding: c.2979C>T
MANE Select: NM_022489
dbSNP: rs372735722
Type: single nucleotide variant
Location: chr14:104713545 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.33 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.34 · 10 PDB
Residue 993: 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

Similar variants

INF2 p.Arg993Gly Uncertain significance ★ ⚠ same residue
INF2 p.Arg993Cys Benign ★ same residue
INF2 p.Arg993His Likely benign ★ same residue
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

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-arg993 (accessed [today's date]).

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