Is INF2 p.Asp591= (c.1773C>T) pathogenic?

INF2 p.Asp591= (c.1773C>T) is classified Benign/Likely benign in INF2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-12-23). Rare (popmax 0.119%, afr); Associated with focal segmental glomerulosclerosis 5.

What condition is associated with INF2 p.Asp591= (c.1773C>T)?

INF2 p.Asp591= (c.1773C>T) is associated with focal segmental glomerulosclerosis 5, Charcot-Marie-Tooth disease dominant intermediate E (ClinVar).

How common is INF2 p.Asp591= (c.1773C>T) in the general population?

INF2 p.Asp591= (c.1773C>T) is rare (popmax 0.119%, afr) (gnomAD).

INF2 p.Asp591=

c.1773C>T · rs201853087 · VCV517839

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.119%, afr)

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 -1.2	GERP -3
Overall
CADD	1.983	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.119% African / African-American · 89/75,044 alleles

Filtering AF 0.0987% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0913%

Overall 0.00645% 104/1,612,508 alleles · rare exomes 50/1,460,200 · genomes 54/152,308 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.119%	843
Admixed American	0.0117%	8,574
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,797
South Asian	0.0022%	45,543
Remaining individualsnot grpmax-eligible	0.0016%	62,464
European (non-Finnish)	0.000254%	393,272

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.Asp591=
Coding: c.1773C>T
MANE Select: NM_022489
dbSNP: rs201853087
Type: single nucleotide variant
Location: chr14:104708473 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.33 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.34 · 10 PDB
Residue 591: the fh2 domain

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.Asp591Asn Likely benign ★★ same residue
INF2 p.Asp591Gly Uncertain significance ★ ⚠ same residue
INF2 p.Asp591His 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-asp591 (accessed [today's date]).

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