Is INF2 p.Ala729= (c.2187C>T) pathogenic?

INF2 p.Ala729= (c.2187C>T) is classified Benign in INF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-04). Very rare (popmax 0.00218%, nfe); Associated with focal segmental glomerulosclerosis 5.

What condition is associated with INF2 p.Ala729= (c.2187C>T)?

INF2 p.Ala729= (c.2187C>T) is associated with focal segmental glomerulosclerosis 5, Charcot-Marie-Tooth disease dominant intermediate E (ClinVar).

How common is INF2 p.Ala729= (c.2187C>T) in the general population?

INF2 p.Ala729= (c.2187C>T) is very rare (popmax 0.00218%, nfe) (gnomAD).

INF2 p.Ala729=

c.2187C>T · rs766576610 · VCV1550702

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00218%, 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	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.8	GERP -2.7
Overall
CADD	5.384	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00218% European (non-Finnish) · 25/1,149,134 alleles

Filtering AF 0.00149% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00126%

Overall 0.0102% 159/1,553,282 alleles · very rare exomes 119/1,401,074 · genomes 40/152,208 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.211%	474
Remaining individualsnot grpmax-eligible	0.0183%	5,477
European (non-Finnish)grpmax	0.00218%	45,965

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala729=
Coding: c.2187C>T
MANE Select: NM_022489
dbSNP: rs766576610
Type: single nucleotide variant
Location: chr14:104710136 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.33 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.34 · 10 PDB
Residue 729: 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.Ala729Thr Conflicting classifications of pathogenicity ★ ⚠ 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-ala729 (accessed [today's date]).

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