Is AVL9 p.Pro15Ser (c.43C>T) pathogenic?

AVL9 p.Pro15Ser (c.43C>T) is classified Uncertain significance in AVL9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-09). AlphaMissense: likely benign (0.1685); Very rare (popmax 0.000202%, nfe).

How common is AVL9 p.Pro15Ser (c.43C>T) in the general population?

AVL9 p.Pro15Ser (c.43C>T) is very rare (popmax 0.000202%, nfe) (gnomAD).

What do computational predictors say about AVL9 p.Pro15Ser (c.43C>T)?

AlphaMissense predicts likely benign (score 0.1685) — an in-silico prediction, not a clinical call.

AVL9 p.Pro15Ser

c.43C>T · VCV4186473

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1685 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000202%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1685	likely benign
REVEL	0.076	moderately benign-leaning
SaProt	LLR -11.27	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.6	phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 88 kb · p 0.00067 · regional, not allelic
Overall
CADD	24.5	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 0.000202% European (non-Finnish) · 2/992,388 alleles

Filtering AF 3.4e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.3e-05%

Overall 0.000181% 2/1,107,118 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: AVL9
Protein: p.Pro15Ser
Coding: c.43C>T
MANE Select: NM_015060
Type: single nucleotide variant
Location: chr7:32495752 (GRCh38)
Gene constraint: LOEUF 0.811 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.73

Full AVL9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AVL9 p.Pro15Ala Uncertain significance ★ ⚠ same residue
AVL9 c.215-1G>A Uncertain significance ★ same type
AVL9 p.Ala510Val Uncertain significance ★ ⚠ same type
AVL9 p.Ala558Val Uncertain significance ★ ⚠ same type
AVL9 p.Arg105Lys Uncertain significance ★ ⚠ same type
AVL9 p.Arg242Gln Uncertain significance ★ ⚠ same type
AVL9 p.Arg242Trp Uncertain significance ★ ⚠ same type
AVL9 p.Arg321Cys 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/avl9-p-pro15ser (accessed [today's date]).

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