Is AVIL p.Ile402Val (c.1204A>G) pathogenic?

AVIL p.Ile402Val (c.1204A>G) is classified Uncertain significance in AVIL (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-06). AlphaMissense: likely benign (0.0904); Absent from gnomAD v4.1; Associated with nephrotic syndrome, type 21.

What condition is associated with AVIL p.Ile402Val (c.1204A>G)?

AVIL p.Ile402Val (c.1204A>G) is associated with nephrotic syndrome, type 21 (ClinVar).

How common is AVIL p.Ile402Val (c.1204A>G) in the general population?

AVIL p.Ile402Val (c.1204A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AVIL p.Ile402Val (c.1204A>G)?

AlphaMissense predicts likely benign (score 0.0904) — an in-silico prediction, not a clinical call.

AVIL p.Ile402Val

c.1204A>G · rs2140450849 · VCV1691303

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0904 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

nephrotic syndrome, type 21

Computational evidence

Protein change
AlphaMissense	0.0904	likely benign
REVEL	0.08	moderately benign-leaning
SaProt	LLR -6.59	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP 2.2, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 18 kb · p 9.4e-05 · regional, not allelic
Overall
CADD	19.03	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AVIL
Protein: p.Ile402Val
Coding: c.1204A>G
MANE Select: NM_006576
dbSNP: rs2140450849
Type: single nucleotide variant
Location: chr12:57807718 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.82 · 1 PDB
Residue 402: 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.Ile402Thr 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-ile402val (accessed [today's date]).

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