Is INF2 p.Cys151Arg (c.451T>C) pathogenic?

INF2 p.Cys151Arg (c.451T>C) is classified Pathogenic/Likely pathogenic in INF2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-30). AlphaMissense: likely pathogenic (0.9794); Absent from gnomAD v4.1; Associated with INF2-related disorder.

What condition is associated with INF2 p.Cys151Arg (c.451T>C)?

INF2 p.Cys151Arg (c.451T>C) is associated with INF2-related disorder, kidney disorder (ClinVar).

How common is INF2 p.Cys151Arg (c.451T>C) in the general population?

INF2 p.Cys151Arg (c.451T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about INF2 p.Cys151Arg (c.451T>C)?

AlphaMissense predicts likely pathogenic (score 0.9794) — an in-silico prediction, not a clinical call.

INF2 p.Cys151Arg

c.451T>C · rs2504241662 · VCV1712412

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9794 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

INF2-related disorder

Computational evidence

Protein change
AlphaMissense	0.9794	likely pathogenic ✓ concordant with ClinVar · top 4% in INF2
REVEL	0.821	moderately pathogenic-leaning
SaProt	LLR -16.76	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 7.1, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 5,444 bp · p 1.4e-07 · regional, not allelic
Overall
CADD	27.5	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.Cys151Arg
Coding: c.451T>C
MANE Select: NM_022489
dbSNP: rs2504241662
Type: single nucleotide variant
Location: chr14:104703164 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.33 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.34 · 10 PDB
Residue 151: 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: kidney disorder

Similar variants

INF2 p.Cys151Tyr Likely pathogenic ★ same residue
INF2 p.Arg214His Pathogenic/Likely pathogenic ★★ same condition
INF2 p.Arg218Gln Pathogenic/Likely pathogenic ★★ same condition
INF2 p.Glu184Lys Pathogenic ★★ same condition
INF2 p.Leu77Pro Pathogenic/Likely pathogenic ★★ same condition
INF2 p.Leu78Pro Likely pathogenic ★★ same condition
INF2 p.Gln903His Uncertain significance ★★ ⚠ same condition
INF2 p.Arg950Trp Benign/Likely benign ★★ ⚠ 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-cys151arg (accessed [today's date]).

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