Is AVIL p.Trp414Ter (c.1241G>A) pathogenic?

AVIL p.Trp414Ter (c.1241G>A) is classified Uncertain significance in AVIL (ClinVar, Single submitter, 1 submitter; last evaluated 2020-07-31). Very rare (popmax 8.47e-05%, nfe); Associated with nephrotic syndrome, type 21.

What condition is associated with AVIL p.Trp414Ter (c.1241G>A)?

AVIL p.Trp414Ter (c.1241G>A) is associated with nephrotic syndrome, type 21 (ClinVar).

How common is AVIL p.Trp414Ter (c.1241G>A) in the general population?

AVIL p.Trp414Ter (c.1241G>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

AVIL p.Trp414Ter

c.1241G>A · VCV3780682

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

nephrotic syndrome, type 21

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 12 of 20
Splicing
SpliceAI	Δ0.62	donor loss at this position · masked 0 · deltas
Pangolin	Δ0.25	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4	GERP 1.1, phastCons 1
Overall
CADD	36.0	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 8.47e-05% European (non-Finnish) · 1/1,180,042 alleles

Overall 6.84e-05% 1/1,461,782 alleles · very rare

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.Trp414Ter
Coding: c.1241G>A
MANE Select: NM_006576
Type: single nucleotide variant
Location: chr12:57807681 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.82 · 1 PDB
Residue 414: 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.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
AVIL c.66+9G>A Uncertain significance ★ 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-trp414ter (accessed [today's date]).

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