Is INF2 p.Phe178Val (c.532T>G) pathogenic?

INF2 p.Phe178Val (c.532T>G) is classified Likely pathogenic in INF2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2017-11-10). AlphaMissense: likely pathogenic (0.9635); Absent from gnomAD v4.1; Associated with nephrotic syndrome.

What condition is associated with INF2 p.Phe178Val (c.532T>G)?

INF2 p.Phe178Val (c.532T>G) is associated with nephrotic syndrome (ClinVar).

How common is INF2 p.Phe178Val (c.532T>G) in the general population?

INF2 p.Phe178Val (c.532T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about INF2 p.Phe178Val (c.532T>G)?

AlphaMissense predicts likely pathogenic (score 0.9635) — an in-silico prediction, not a clinical call.

INF2 p.Phe178Val

c.532T>G · rs2140648131 · VCV1344689

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9635 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

nephrotic syndrome

Computational evidence

Protein change
AlphaMissense	0.9635	likely pathogenic ✓ concordant with ClinVar · top 5% in INF2
REVEL	0.895	moderately pathogenic-leaning
SaProt	LLR -15.93	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 7, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 5,444 bp · p 1.4e-07 · regional, not allelic
Overall
CADD	27.0	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.Phe178Val
Coding: c.532T>G
MANE Select: NM_022489
dbSNP: rs2140648131
Type: single nucleotide variant
Location: chr14:104703319 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.33 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.34 · 10 PDB
Residue 178: the gbd/fh3 domain

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

Disease context

nephrotic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

INF2 p.Arg1045Trp Conflicting classifications of pathogenicity ★ ⚠ same condition
INF2 p.Glu863Ter Uncertain significance same condition
INF2 p.Arg177Cys Pathogenic/Likely pathogenic ★★ same type
INF2 p.Arg214Cys Pathogenic/Likely pathogenic ★★ same type
INF2 p.Arg214His Pathogenic/Likely pathogenic ★★ same type
INF2 p.Arg218Gln Pathogenic/Likely pathogenic ★★ same type
INF2 p.Arg218Trp Pathogenic/Likely pathogenic ★★ same type
INF2 p.Arg91Gly Pathogenic/Likely pathogenic ★★ same type

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-phe178val (accessed [today's date]).

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