Is AVIL p.Glu507Lys (c.1519G>A) pathogenic?

AVIL p.Glu507Lys (c.1519G>A) is classified Uncertain significance in AVIL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-15). AlphaMissense: likely benign (0.0862); Ultra-rare (popmax 0.016%, afr).

How common is AVIL p.Glu507Lys (c.1519G>A) in the general population?

AVIL p.Glu507Lys (c.1519G>A) is ultra-rare (popmax 0.016%, afr) (gnomAD).

What do computational predictors say about AVIL p.Glu507Lys (c.1519G>A)?

AlphaMissense predicts likely benign (score 0.0862) — an in-silico prediction, not a clinical call.

AVIL p.Glu507Lys

c.1519G>A · rs367900033 · VCV2283043

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0862 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.016%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0862	likely benign
REVEL	0.096	moderately benign-leaning
SaProt	LLR -6.96	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 4.9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 18 kb · p 9.4e-05 · regional, not allelic
Overall
CADD	24.5	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

Grpmax group 0.016% African / African-American · 12/74,906 alleles

Filtering AF 0.00922% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00722%

Overall 0.00136% 22/1,613,964 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.016%	6,242
Admixed American	0.005%	19,995
Remaining individualsnot grpmax-eligible	0.0016%	62,480
South Asian	0.0011%	91,078
European (non-Finnish)	0.000424%	236,003

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.Glu507Lys
Coding: c.1519G>A
MANE Select: NM_006576
dbSNP: rs367900033
Type: single nucleotide variant
Location: chr12:57806512 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.82 · 1 PDB
Residue 507: the 'core' region

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

Similar variants

AVIL p.Arg199Ter Likely pathogenic ★★ same type
AVIL p.Asn777Lys Uncertain significance ★★ ⚠ same type
AVIL p.Gly577Ser Uncertain significance ★★ ⚠ same type
AVIL p.Gly626Ser Uncertain significance ★★ ⚠ same type
AVIL p.Ile250Thr Uncertain significance ★★ ⚠ same type
AVIL c.1194+202C>T Benign ★★ same type
AVIL c.2151+142A>G Benign ★★ same type
AVIL c.67-155C>T Benign ★★ same type

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-glu507lys (accessed [today's date]).

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