Is INF2 p.Cys484= (c.1452T>C) pathogenic?

INF2 p.Cys484= (c.1452T>C) is classified Benign/Likely benign in INF2 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-01-25). Low-frequency (popmax 3.87%, afr); Associated with kidney disorder.

What condition is associated with INF2 p.Cys484= (c.1452T>C)?

INF2 p.Cys484= (c.1452T>C) is associated with kidney disorder, focal segmental glomerulosclerosis 5, Charcot-Marie-Tooth disease dominant intermediate E (ClinVar).

How common is INF2 p.Cys484= (c.1452T>C) in the general population?

INF2 p.Cys484= (c.1452T>C) is low-frequency (popmax 3.87%, afr) (gnomAD).

INF2 p.Cys484=

c.1452T>C · rs371775604 · VCV383168

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.87%, afr)

Conditions

kidney disorder

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 -7.3	GERP -0.36
Overall
CADD	1.199	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.87% African / African-American · 2,069/53,458 alleles

Filtering AF 3.73% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.68%

Overall 0.275% 2,998/1,090,012 alleles · low-frequency exomes 1,744/966,872 · genomes 1,254/123,140 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.87%	26
Middle Eastern	0.75%	133
Admixed American	0.461%	217
Remaining individualsnot grpmax-eligible	0.451%	222
European (non-Finnish)	0.0631%	1,585
Finnishnot grpmax-eligible	0.0413%	2,424
Ashkenazi Jewishnot grpmax-eligible	0.0405%	2,471
South Asian	0.00923%	10,840

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.Cys484=
Coding: c.1452T>C
MANE Select: NM_022489
dbSNP: rs371775604
Type: single nucleotide variant
Location: chr14:104707719 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.33 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.34 · 10 PDB
Residue 484: the 'disordered' region

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

Disease context

kidney disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: focal segmental glomerulosclerosis 5 Charcot-Marie-Tooth disease dominant intermediate E

Similar variants

INF2 p.Cys484Tyr Benign/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
INF2 p.Arg91Gly Pathogenic/Likely pathogenic ★★ same condition
INF2 p.Asn202Asp 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-cys484 (accessed [today's date]).

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