Is AVIL p.Asp41fs (c.121del) pathogenic?

AVIL p.Asp41fs (c.121del) is classified Likely pathogenic in AVIL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-18). Ultra-rare (popmax 0.0217%, amr); Associated with nephrotic syndrome, type 21.

What condition is associated with AVIL p.Asp41fs (c.121del)?

AVIL p.Asp41fs (c.121del) is associated with nephrotic syndrome, type 21 (ClinVar).

How common is AVIL p.Asp41fs (c.121del) in the general population?

AVIL p.Asp41fs (c.121del) is ultra-rare (popmax 0.0217%, amr) (gnomAD).

AVIL p.Asp41fs

c.121del · VCV4850182

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0217%, amr)

Conditions

nephrotic syndrome, type 21

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 2.3, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0217% Admixed American · 13/59,858 alleles

Filtering AF 0.0128% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0102%

Overall 0.00143% 23/1,612,650 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0217%	4,604
Remaining individualsnot grpmax-eligible	0.0048%	20,821
European (non-Finnish)	0.000593%	168,530

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: AVIL
Protein: p.Asp41fs
Coding: c.121del
MANE Select: NM_006576
Type: Deletion
Location: chr12:57814172 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.82 · 1 PDB
Residue 41: the 'core' region

Full AVIL gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

nephrotic syndrome, type 21 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AVIL p.Asp41Asn Uncertain significance ★ ⚠ same residue
AVIL p.Arg199Ter Likely pathogenic ★★ same condition
AVIL p.Asn777Lys Uncertain significance ★★ ⚠ same condition
AVIL p.Ile250Thr Uncertain significance ★★ ⚠ same condition
AVIL p.Lys204Glu Benign/Likely benign ★★ same condition
AVIL p.Arg135Gln Likely pathogenic ★ ⚠ same condition
AVIL p.Glu584Ter Likely pathogenic ★ same condition
AVIL p.Lys169Ter 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/avil-p-asp41fs (accessed [today's date]).

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