Is INF2 p.Pro493Arg (c.1478C>G) pathogenic?

INF2 p.Pro493Arg (c.1478C>G) is classified Uncertain significance in INF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-05). AlphaMissense: likely benign (0.1719); Very rare (popmax 0.000101%, nfe).

How common is INF2 p.Pro493Arg (c.1478C>G) in the general population?

INF2 p.Pro493Arg (c.1478C>G) is very rare (popmax 0.000101%, nfe) (gnomAD).

What do computational predictors say about INF2 p.Pro493Arg (c.1478C>G)?

AlphaMissense predicts likely benign (score 0.1719) — an in-silico prediction, not a clinical call.

INF2 p.Pro493Arg

c.1478C>G · VCV4882971

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1719 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000101%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1719	likely benign
REVEL	0.355	indeterminate
SaProt	LLR -12.35	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.37	GERP 4.2
Regional constraint	o/e 1.23	unconstrained · MANE · 929 bp · p 5.5e-05 · regional, not allelic
Overall
CADD	15.07	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

Grpmax group 0.000101% European (non-Finnish) · 1/986,454 alleles

Overall 7.39e-05% 1/1,353,142 alleles · very rare exomes 0/1,214,522 · genomes 1/138,620 · joint denominator

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.Pro493Arg
Coding: c.1478C>G
MANE Select: NM_022489
Type: single nucleotide variant
Location: chr14:104707745 (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

Similar variants

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
INF2 p.Asn202Asp Likely pathogenic ★★ same type
INF2 p.Cys151Arg 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-pro493arg (accessed [today's date]).

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