Is INF2 p.Pro1096Ser (c.3286C>T) pathogenic?

INF2 p.Pro1096Ser (c.3286C>T) is classified Benign in INF2 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0724); Common (popmax 11.5%, mid) — too common for a highly-penetrant pathogenic allele; Associated with focal segmental glomerulosclerosis 5.

What condition is associated with INF2 p.Pro1096Ser (c.3286C>T)?

INF2 p.Pro1096Ser (c.3286C>T) is associated with focal segmental glomerulosclerosis 5, Charcot-Marie-Tooth disease dominant intermediate E (ClinVar).

What do computational predictors say about INF2 p.Pro1096Ser (c.3286C>T)?

AlphaMissense predicts likely benign (score 0.0724) — an in-silico prediction, not a clinical call.

INF2 p.Pro1096Ser

Q: How common is INF2 p.Pro1096Ser (c.3286C>T) in the general population?

INF2 p.Pro1096Ser (c.3286C>T) is common (popmax 11.5%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3286C>T · rs34251364 · VCV261619

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

AlphaMissense

likely benign

0.0724 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 11.5%, mid) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

focal segmental glomerulosclerosis 5

Computational evidence

Protein change
AlphaMissense	0.0724	likely benign
REVEL	0.092	moderately benign-leaning
SaProt	LLR -6.60	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP 5.7, phastCons 0.051
Regional constraint	o/e 1.03	unconstrained · MANE · 1,758 bp · p 0.55 · regional, not allelic
Overall
CADD	14.77	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 11.5% Middle Eastern · 695/6,060 alleles

Filtering AF 10.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 10.5%

Overall 7.51% 120,986/1,611,110 alleles · common exomes 111,902/1,458,830 · genomes 9,084/152,280 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	11.5%	9
Ashkenazi Jewishnot grpmax-eligible	10.4%	10
European (non-Finnish)	8.19%	12
South Asian	8.17%	12
Remaining individualsnot grpmax-eligible	7.88%	13
Amishnot grpmax-eligible	6.91%	14
Admixed American	4.96%	20
Finnishnot grpmax-eligible	4.87%	21
African / African-American	1.99%	50
East Asian	1.59%	63

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.Pro1096Ser
Coding: c.3286C>T
MANE Select: NM_022489
dbSNP: rs34251364
Type: single nucleotide variant
Location: chr14:104714448 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.33 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.34 · 10 PDB
Residue 1096: a UniProt-annotated variant site (in)

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

Disease context

focal segmental glomerulosclerosis 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Charcot-Marie-Tooth disease dominant intermediate E

Similar variants

INF2 p.Pro1096Arg Uncertain significance ★ ⚠ 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-pro1096ser (accessed [today's date]).

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