Is INF2 p.Ser1042= (c.3126C>T) pathogenic?

INF2 p.Ser1042= (c.3126C>T) is classified Conflicting classifications of pathogenicity in INF2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-12-12). Ultra-rare (popmax 0.0826%, mid); Associated with focal segmental glomerulosclerosis 5.

What condition is associated with INF2 p.Ser1042= (c.3126C>T)?

INF2 p.Ser1042= (c.3126C>T) is associated with focal segmental glomerulosclerosis 5, Charcot-Marie-Tooth disease dominant intermediate E (ClinVar).

How common is INF2 p.Ser1042= (c.3126C>T) in the general population?

INF2 p.Ser1042= (c.3126C>T) is ultra-rare (popmax 0.0826%, mid) (gnomAD).

INF2 p.Ser1042=

c.3126C>T · rs1035033414 · VCV540050

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0826%, mid)

Conditions

focal segmental glomerulosclerosis 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.24	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP -2.9	GERP -16
Overall
CADD	1.815	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0826% Middle Eastern · 5/6,054 alleles

Filtering AF 0.0325% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0211%

Overall 0.0022% 35/1,592,448 alleles · ultra-rare exomes 34/1,440,240 · genomes 1/152,208 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0826%	1,211
Remaining individualsnot grpmax-eligible	0.00487%	20,554
Admixed American	0.00348%	28,730
East Asian	0.00229%	43,652
South Asian	0.00228%	43,907
European (non-Finnish)	0.00179%	55,758
African / African-American	0.00134%	74,356

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.Ser1042=
Coding: c.3126C>T
MANE Select: NM_022489
dbSNP: rs1035033414
Type: single nucleotide variant
Location: chr14:104714288 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.33 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.34 · 10 PDB
Residue 1042: 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-ser1042 (accessed [today's date]).

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