Is INF2 p.His683= (c.2049C>T) pathogenic?

INF2 p.His683= (c.2049C>T) is classified Likely benign in INF2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-29). Very rare (popmax 0.00333%, amr); Associated with focal segmental glomerulosclerosis 5.

What condition is associated with INF2 p.His683= (c.2049C>T)?

INF2 p.His683= (c.2049C>T) is associated with focal segmental glomerulosclerosis 5, Charcot-Marie-Tooth disease dominant intermediate E (ClinVar).

How common is INF2 p.His683= (c.2049C>T) in the general population?

INF2 p.His683= (c.2049C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

INF2 p.His683=

c.2049C>T · rs760045317 · VCV540063

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

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
Constraint at this position
Conservation	phyloP -9.5	GERP -5.2
Overall
CADD	2.341	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,008 alleles

Filtering AF 0.000689% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.00124% 20/1,611,648 alleles · very rare exomes 20/1,459,368 · genomes 0/152,280 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,004
East Asian	0.00223%	44,874
South Asian	0.0022%	45,519
African / African-American	0.00133%	75,004
European (non-Finnish)	0.00119%	84,195

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.His683=
Coding: c.2049C>T
MANE Select: NM_022489
dbSNP: rs760045317
Type: single nucleotide variant
Location: chr14:104709380 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.33 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.34 · 10 PDB
Residue 683: the fh2 domain; an α-helix

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-his683 (accessed [today's date]).

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