Is AVEN p.Gly9Glu (c.26G>A) pathogenic?

AVEN p.Gly9Glu (c.26G>A) is classified Uncertain significance in AVEN (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-17). AlphaMissense: likely pathogenic (0.5684); Very rare (popmax 0.00141%, nfe).

How common is AVEN p.Gly9Glu (c.26G>A) in the general population?

AVEN p.Gly9Glu (c.26G>A) is very rare (popmax 0.00141%, nfe) (gnomAD).

What do computational predictors say about AVEN p.Gly9Glu (c.26G>A)?

AlphaMissense predicts likely pathogenic (score 0.5684) — an in-silico prediction, not a clinical call.

AVEN p.Gly9Glu

c.26G>A · rs1410624797 · VCV2251618

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5684 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00141%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5684	likely pathogenic
REVEL	0.208	benign-leaning
SaProt	LLR -11.03	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.30 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.5	GERP 1.3, phastCons 1
Regional constraint	o/e 1.38	unconstrained · MANE · 172 kb · p 2.1e-15 · regional, not allelic
Overall
CADD	18.55	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 0.00141% European (non-Finnish) · 13/920,006 alleles

Filtering AF 0.000788% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000607%

Overall 0.00116% 13/1,122,720 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: AVEN
Protein: p.Gly9Glu
Coding: c.26G>A
MANE Select: NM_020371
dbSNP: rs1410624797
Type: single nucleotide variant
Location: chr15:34039021 (GRCh38)
Gene constraint: LOEUF 1.172 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.86
Residue 9: the 'disordered' region

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

Similar variants

CHRM5 p.Ala9Gly Uncertain significance ★ ⚠ same residue
RYR3 p.Ala4568Pro Uncertain significance ★★ ⚠ same type
RYR3 p.Ala4594Val Uncertain significance ★★ ⚠ same type
RYR3 p.Ala4650Thr Uncertain significance ★★ ⚠ same type
RYR3 p.Arg4862His Uncertain significance ★★ ⚠ same type
RYR3 p.Glu4573Gln Uncertain significance ★★ same type
RYR3 p.His4609Arg Uncertain significance ★★ ⚠ same type
RYR3 p.Ile4604Thr Uncertain significance ★★ ⚠ 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/aven-p-gly9glu (accessed [today's date]).

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