Is AVIL p.Lys204Glu (c.610A>G) pathogenic?

AVIL p.Lys204Glu (c.610A>G) is classified Benign/Likely benign in AVIL (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-11-27). AlphaMissense: likely benign (0.0526); Common (popmax 100%, mid) — too common for a highly-penetrant pathogenic allele; Associated with nephrotic syndrome, type 21.

What condition is associated with AVIL p.Lys204Glu (c.610A>G)?

AVIL p.Lys204Glu (c.610A>G) is associated with nephrotic syndrome, type 21 (ClinVar).

What do computational predictors say about AVIL p.Lys204Glu (c.610A>G)?

AlphaMissense predicts likely benign (score 0.0526) — an in-silico prediction, not a clinical call.

AVIL p.Lys204Glu

Q: How common is AVIL p.Lys204Glu (c.610A>G) in the general population?

AVIL p.Lys204Glu (c.610A>G) is common (popmax 100%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.610A>G · rs2172521 · VCV1192376

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0526 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 100%, mid) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

nephrotic syndrome, type 21

Computational evidence

Protein change
AlphaMissense	0.0526	likely benign
REVEL	0.166	moderately benign-leaning
SaProt	LLR -6.24	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 3.3	GERP 0.057, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 18 kb · p 9.4e-05 · regional, not allelic
Overall
CADD	16.47	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 100% Middle Eastern · 6,044/6,044 alleles

Filtering AF 99.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 99.8%

Overall 100% 1,614,154/1,614,162 alleles · common

Ancestry group	Frequency	1 in
Admixed American	100%	1
East Asian	100%	1
South Asian	100%	1
Finnishnot grpmax-eligible	100%	1
Ashkenazi Jewishnot grpmax-eligible	100%	1
Amishnot grpmax-eligible	100%	1
Middle Easterngrpmax	100%	1
Remaining individualsnot grpmax-eligible	100%	1
European (non-Finnish)	100%	1
African / African-American	100%	1

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.Lys204Glu
Coding: c.610A>G
MANE Select: NM_006576
dbSNP: rs2172521
Type: single nucleotide variant
Location: chr12:57810500 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.82 · 1 PDB
Residue 204: a UniProt-annotated variant site (in); 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.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
AVIL p.Asn144Ile 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-lys204glu (accessed [today's date]).

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