Is INF2 p.Ser186Pro (c.556T>C) pathogenic?

INF2 p.Ser186Pro (c.556T>C) is classified Likely pathogenic in INF2 (ClinVar, Single submitter, 3 submitters; last evaluated 2024-11-01). AlphaMissense: ambiguous (0.4387); Absent from gnomAD v4.1; Associated with INF2-related disorder.

What condition is associated with INF2 p.Ser186Pro (c.556T>C)?

INF2 p.Ser186Pro (c.556T>C) is associated with INF2-related disorder, focal segmental glomerulosclerosis 5 (ClinVar).

How common is INF2 p.Ser186Pro (c.556T>C) in the general population?

INF2 p.Ser186Pro (c.556T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about INF2 p.Ser186Pro (c.556T>C)?

AlphaMissense predicts ambiguous (score 0.4387) — an in-silico prediction, not a clinical call.

INF2 p.Ser186Pro

c.556T>C · rs267606877 · VCV1050

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.4387 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

INF2-related disorder

Computational evidence

Protein change
AlphaMissense	0.4387	ambiguous
REVEL	0.636	indeterminate
SaProt	LLR -13.82	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP 4.4, phastCons 0.8
Regional constraint	o/e 0.72	unconstrained · MANE · 5,444 bp · p 1.4e-07 · regional, not allelic
Overall
CADD	20.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: INF2
Protein: p.Ser186Pro
Coding: c.556T>C
MANE Select: NM_022489
dbSNP: rs267606877
Type: single nucleotide variant
Location: chr14:104703343 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.33 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.34 · 10 PDB
Residue 186: the gbd/fh3 domain; a UniProt-annotated variant site (in fsgs5)

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

Similar variants

INF2 p.Ser186= 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-ser186pro (accessed [today's date]).

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