Is AVIL p.Arg199Ter (c.595C>T) pathogenic?

AVIL p.Arg199Ter (c.595C>T) is classified Likely pathogenic in AVIL (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-10-04). Rare (popmax 0.245%, afr); Associated with nephrotic syndrome, type 21.

What condition is associated with AVIL p.Arg199Ter (c.595C>T)?

AVIL p.Arg199Ter (c.595C>T) is associated with nephrotic syndrome, type 21, nephrotic syndrome (ClinVar).

How common is AVIL p.Arg199Ter (c.595C>T) in the general population?

AVIL p.Arg199Ter (c.595C>T) is rare (popmax 0.245%, afr) (gnomAD).

AVIL p.Arg199Ter

c.595C>T · rs138728046 · VCV1810257

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.245%, afr)

Conditions

nephrotic syndrome, type 21

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 20
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	GERP 1.2, phastCons 1
Overall
CADD	41.0	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 0.245% African / African-American · 184/75,004 alleles

Filtering AF 0.216% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.205%

Overall 0.0209% 338/1,613,922 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.245%	408
South Asian	0.0648%	1,543
Middle Eastern	0.0503%	1,989
Remaining individualsnot grpmax-eligible	0.048%	2,083
Admixed American	0.0183%	5,456
European (non-Finnish)	0.00424%	23,600
East Asian	0.00223%	44,872

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.Arg199Ter
Coding: c.595C>T
MANE Select: NM_006576
dbSNP: rs138728046
Type: single nucleotide variant
Location: chr12:57810515 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.82 · 1 PDB
Residue 199: 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

Also linked: nephrotic syndrome

Similar variants

AVIL p.Arg199Gln Uncertain significance ★ ⚠ same residue
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-arg199ter (accessed [today's date]).

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