Is AVL9 p.Ser613Pro (c.1837T>C) pathogenic?

AVL9 p.Ser613Pro (c.1837T>C) is classified Uncertain significance in AVL9 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-17). AlphaMissense: likely pathogenic (0.9572); Very rare (popmax 0.00705%, nfe).

How common is AVL9 p.Ser613Pro (c.1837T>C) in the general population?

AVL9 p.Ser613Pro (c.1837T>C) is very rare (popmax 0.00705%, nfe) (gnomAD).

What do computational predictors say about AVL9 p.Ser613Pro (c.1837T>C)?

AlphaMissense predicts likely pathogenic (score 0.9572) — an in-silico prediction, not a clinical call.

AVL9 p.Ser613Pro

c.1837T>C · rs187363596 · VCV2251864

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9572 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00705%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9572	likely pathogenic
REVEL	0.124	moderately benign-leaning
SaProt	LLR -11.43	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 88 kb · p 0.00067 · regional, not allelic
Overall
CADD	29.7	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 0.00705% European (non-Finnish) · 83/1,177,608 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00534%

Overall 0.00559% 90/1,611,204 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00962%	10,398
European (non-Finnish)grpmax	0.00705%	14,188
African / African-American	0.00133%	74,940

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser613Pro
Coding: c.1837T>C
MANE Select: NM_015060
dbSNP: rs187363596
Type: single nucleotide variant
Location: chr7:32583797 (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 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
AVL9 p.Arg427Gln 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-ser613pro (accessed [today's date]).

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