Is INF2 p.Ser372Phe (c.1115C>T) pathogenic?

INF2 p.Ser372Phe (c.1115C>T) is classified Likely benign in INF2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-10-17). AlphaMissense: likely benign (0.0754); Ultra-rare (popmax 0.061%, amr); Associated with focal segmental glomerulosclerosis 5.

What condition is associated with INF2 p.Ser372Phe (c.1115C>T)?

INF2 p.Ser372Phe (c.1115C>T) is associated with focal segmental glomerulosclerosis 5, Charcot-Marie-Tooth disease dominant intermediate E (ClinVar).

How common is INF2 p.Ser372Phe (c.1115C>T) in the general population?

INF2 p.Ser372Phe (c.1115C>T) is ultra-rare (popmax 0.061%, amr) (gnomAD).

What do computational predictors say about INF2 p.Ser372Phe (c.1115C>T)?

AlphaMissense predicts likely benign (score 0.0754) — an in-silico prediction, not a clinical call.

INF2 p.Ser372Phe

c.1115C>T · rs770882784 · VCV246490

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0754 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.061%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

focal segmental glomerulosclerosis 5

Computational evidence

Protein change
AlphaMissense	0.0754	likely benign
REVEL	0.272	benign-leaning
SaProt	LLR -8.98	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 -0.89	GERP 3
Regional constraint	o/e 1.23	unconstrained · MANE · 929 bp · p 5.5e-05 · regional, not allelic
Overall
CADD	10.2	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 0.061% Admixed American · 35/57,388 alleles

Filtering AF 0.045% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0396%

Overall 0.00226% 36/1,592,202 alleles · ultra-rare exomes 34/1,440,206 · genomes 2/151,996 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.061%	1,640
European (non-Finnish)	8.54e-05%	1,170,894

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.Ser372Phe
Coding: c.1115C>T
MANE Select: NM_022489
dbSNP: rs770882784
Type: single nucleotide variant
Location: chr14:104707382 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.33 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.34 · 10 PDB
Residue 372: 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.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
INF2 p.Glu184Lys 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-ser372phe (accessed [today's date]).

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