Is INF2 p.Pro1069Leu (c.3206C>T) pathogenic?

INF2 p.Pro1069Leu (c.3206C>T) is classified Likely benign in INF2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-26). AlphaMissense: likely benign (0.072); Ultra-rare (popmax 0.0246%, nfe); Associated with focal segmental glomerulosclerosis 5.

What condition is associated with INF2 p.Pro1069Leu (c.3206C>T)?

INF2 p.Pro1069Leu (c.3206C>T) is associated with focal segmental glomerulosclerosis 5, Charcot-Marie-Tooth disease dominant intermediate E (ClinVar).

How common is INF2 p.Pro1069Leu (c.3206C>T) in the general population?

INF2 p.Pro1069Leu (c.3206C>T) is ultra-rare (popmax 0.0246%, nfe) (gnomAD).

What do computational predictors say about INF2 p.Pro1069Leu (c.3206C>T)?

AlphaMissense predicts likely benign (score 0.072) — an in-silico prediction, not a clinical call.

INF2 p.Pro1069Leu

c.3206C>T · rs376139171 · VCV312708

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.072 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0246%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

focal segmental glomerulosclerosis 5

Computational evidence

Protein change
AlphaMissense	0.072	likely benign
REVEL	0.158	moderately benign-leaning
SaProt	LLR -6.87	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	GERP 4.1, phastCons 0.004
Regional constraint	o/e 1.03	unconstrained · MANE · 1,758 bp · p 0.55 · regional, not allelic
Overall
CADD	13.55	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 0.0246% European (non-Finnish) · 288/1,172,900 alleles

Filtering AF 0.0222% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0213%

Overall 0.0191% 305/1,597,666 alleles · ultra-rare exomes 285/1,445,520 · genomes 20/152,146 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0246%	4,073
Remaining individualsnot grpmax-eligible	0.0145%	6,874
African / African-American	0.00939%	10,650
East Asian	0.00227%	44,002

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.Pro1069Leu
Coding: c.3206C>T
MANE Select: NM_022489
dbSNP: rs376139171
Type: single nucleotide variant
Location: chr14:104714368 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.33 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.34 · 10 PDB
Residue 1069: the 'disordered' region

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.Pro1069= Benign/Likely benign ★★ same residue
INF2 p.Pro1069Ser 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

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-pro1069leu (accessed [today's date]).

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