Is INF2 p.Arg604= (c.1812A>T) pathogenic?

INF2 p.Arg604= (c.1812A>T) is classified Conflicting classifications of pathogenicity in INF2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-05-09). Ultra-rare (popmax 0.0822%, mid); Associated with kidney disorder.

What condition is associated with INF2 p.Arg604= (c.1812A>T)?

INF2 p.Arg604= (c.1812A>T) is associated with kidney disorder, focal segmental glomerulosclerosis 5, Charcot-Marie-Tooth disease dominant intermediate E (ClinVar).

How common is INF2 p.Arg604= (c.1812A>T) in the general population?

INF2 p.Arg604= (c.1812A>T) is ultra-rare (popmax 0.0822%, mid) (gnomAD).

INF2 p.Arg604=

c.1812A>T · rs758465730 · VCV1712418

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0822%, mid)

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 2.5	GERP 1.1, phastCons 1
Overall
CADD	8.109	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0822% Middle Eastern · 5/6,084 alleles

Filtering AF 0.0323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.021%

Overall 0.000992% 16/1,612,254 alleles · ultra-rare exomes 15/1,460,266 · genomes 1/151,988 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0822%	1,217
African / African-American	0.012%	8,318
Remaining individualsnot grpmax-eligible	0.0032%	31,221

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.Arg604=
Coding: c.1812A>T
MANE Select: NM_022489
dbSNP: rs758465730
Type: single nucleotide variant
Location: chr14:104708512 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.33 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.34 · 10 PDB
Residue 604: the fh2 domain; an α-helix

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.Arg604Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
INF2 p.Arg604Ter Uncertain significance ★ 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

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-arg604 (accessed [today's date]).

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