Is INF2 p.Ser607= (c.1821C>A) pathogenic?

INF2 p.Ser607= (c.1821C>A) is classified Likely benign in INF2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-09-18). Very rare (popmax 0.00322%, nfe); Associated with focal segmental glomerulosclerosis 5.

What condition is associated with INF2 p.Ser607= (c.1821C>A)?

INF2 p.Ser607= (c.1821C>A) is associated with focal segmental glomerulosclerosis 5, Charcot-Marie-Tooth disease dominant intermediate E (ClinVar).

How common is INF2 p.Ser607= (c.1821C>A) in the general population?

INF2 p.Ser607= (c.1821C>A) is very rare (popmax 0.00322%, nfe) (gnomAD).

INF2 p.Ser607=

c.1821C>A · rs751949801 · VCV472839

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00322%, nfe)

Conditions

focal segmental glomerulosclerosis 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.31 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.034	GERP 1.5, phastCons 0.87
Overall
CADD	8.735	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00322% European (non-Finnish) · 38/1,179,818 alleles

Filtering AF 0.00239% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0021%

Overall 0.00248% 40/1,612,406 alleles · very rare exomes 37/1,460,258 · genomes 3/152,148 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00322%	31,048
Remaining individualsnot grpmax-eligible	0.0016%	62,446
African / African-American	0.00133%	74,908

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.Ser607=
Coding: c.1821C>A
MANE Select: NM_022489
dbSNP: rs751949801
Type: single nucleotide variant
Location: chr14:104708521 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.33 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.34 · 10 PDB
Residue 607: the fh2 domain

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.Ser607Cys 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-ser607 (accessed [today's date]).

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