Is INF2 p.Ala728= (c.2184C>T) pathogenic?

INF2 p.Ala728= (c.2184C>T) is classified Likely benign in INF2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-05-24). Ultra-rare (popmax 0.0122%, eas); Associated with Inborn genetic diseases.

What condition is associated with INF2 p.Ala728= (c.2184C>T)?

INF2 p.Ala728= (c.2184C>T) is associated with Inborn genetic diseases, focal segmental glomerulosclerosis 5, Charcot-Marie-Tooth disease dominant intermediate E (ClinVar).

How common is INF2 p.Ala728= (c.2184C>T) in the general population?

INF2 p.Ala728= (c.2184C>T) is ultra-rare (popmax 0.0122%, eas) (gnomAD).

INF2 p.Ala728=

c.2184C>T · rs564499884 · VCV540060

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0122%, eas)

Conditions

Inborn genetic diseases

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 -2.4	GERP 0.68
Overall
CADD	7.269	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0122% East Asian · 5/41,138 alleles

Filtering AF 0.00477% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00307%

Overall 0.0029% 45/1,553,330 alleles · ultra-rare exomes 38/1,400,990 · genomes 7/152,340 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0122%	8,228
South Asian	0.00356%	28,072
Remaining individualsnot grpmax-eligible	0.00332%	30,133
European (non-Finnish)	0.00287%	34,820
African / African-American	0.00273%	36,657

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.Ala728=
Coding: c.2184C>T
MANE Select: NM_022489
dbSNP: rs564499884
Type: single nucleotide variant
Location: chr14:104710133 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.33 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.34 · 10 PDB
Residue 728: the fh2 domain; an α-helix

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

Disease context

Inborn genetic diseases — 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.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-ala728 (accessed [today's date]).

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