Is INF2 p.Pro495= (c.1485G>A) pathogenic?

INF2 p.Pro495= (c.1485G>A) is classified Conflicting classifications of pathogenicity in INF2 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-11-12). Ultra-rare (popmax 0.0112%, eas); Associated with INF2-related disorder.

What condition is associated with INF2 p.Pro495= (c.1485G>A)?

INF2 p.Pro495= (c.1485G>A) is associated with INF2-related disorder, focal segmental glomerulosclerosis 5, Charcot-Marie-Tooth disease dominant intermediate E (ClinVar).

How common is INF2 p.Pro495= (c.1485G>A) in the general population?

INF2 p.Pro495= (c.1485G>A) is ultra-rare (popmax 0.0112%, eas) (gnomAD).

INF2 p.Pro495=

c.1485G>A · rs780642540 · VCV651536

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0112%, eas)

Conditions

INF2-related 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 -15	GERP -7.4
Overall
CADD	0.136	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0112% East Asian · 3/26,690 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0046%

Overall 0.00644% 67/1,040,164 alleles · ultra-rare exomes 62/948,140 · genomes 5/92,024 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0112%	8,897
South Asian	0.011%	9,069
African / African-American	0.00867%	11,528
European (non-Finnish)	0.00663%	15,093
Remaining individualsnot grpmax-eligible	0.00487%	20,548

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.Pro495=
Coding: c.1485G>A
MANE Select: NM_022489
dbSNP: rs780642540
Type: single nucleotide variant
Location: chr14:104707752 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.33 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.34 · 10 PDB

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

Disease context

INF2-related disorder

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

Similar variants

INF2 p.Pro495Leu 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
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-pro495 (accessed [today's date]).

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