Is INF2 p.Arg9Ser (c.25C>A) pathogenic?

INF2 p.Arg9Ser (c.25C>A) is classified Uncertain significance in INF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-07-02). AlphaMissense: ambiguous (0.3454); No allele count reported in gnomAD v4.1 (AN 1,590,374).

How common is INF2 p.Arg9Ser (c.25C>A) in the general population?

INF2 p.Arg9Ser (c.25C>A) is no allele count reported in gnomAD v4.1 (AN 1,590,374) (gnomAD).

What do computational predictors say about INF2 p.Arg9Ser (c.25C>A)?

AlphaMissense predicts ambiguous (score 0.3454) — an in-silico prediction, not a clinical call.

INF2 p.Arg9Ser

c.25C>A · rs1889485557 · VCV1312837

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3454 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,590,374)

Computational evidence

Protein change
AlphaMissense	0.3454	ambiguous
REVEL	0.39	indeterminate
SaProt	LLR -6.82	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 7, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 99 bp · p 0.8 · regional, not allelic
Overall
CADD	25.3	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

No allele count reported in gnomAD v4.1 (AN 1,590,374). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: INF2
Protein: p.Arg9Ser
Coding: c.25C>A
MANE Select: NM_022489
dbSNP: rs1889485557
Type: single nucleotide variant
Location: chr14:104701390 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.33 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.34 · 10 PDB
Residue 9: the gbd/fh3 domain; the 'disordered' region; an α-helix

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

Similar variants

INF2 p.Arg9Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
INF2 p.Arg9Pro Uncertain significance ★ same residue
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-arg9ser (accessed [today's date]).

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