Is AGBL5 p.Ser651Ter (c.1950dup) pathogenic?

AGBL5 p.Ser651Ter (c.1950dup) is classified Pathogenic in AGBL5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-20). Very rare (popmax 0.00229%, nfe).

How common is AGBL5 p.Ser651Ter (c.1950dup) in the general population?

AGBL5 p.Ser651Ter (c.1950dup) is very rare (popmax 0.00229%, nfe) (gnomAD).

AGBL5 p.Ser651Ter

c.1950dup · rs772873071 · VCV2784135

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00229%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 11 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.1	GERP 1.3, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00229% European (non-Finnish) · 27/1,180,046 alleles

Filtering AF 0.00157% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00134%

Overall 0.00173% 28/1,614,098 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00229%	43,705
Remaining individualsnot grpmax-eligible	0.0016%	62,490

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: AGBL5
Protein: p.Ser651Ter
Coding: c.1950dup
MANE Select: NM_021831
dbSNP: rs772873071
Type: Duplication
Location: chr2:27059264 (GRCh38)
Gene constraint: LOEUF 0.709 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.36 · 10 PDB
Residue 651: a UniProt-annotated variant site (found in patients with a usher-like phenotype encompassing rp and hearing loss; likely pathogenic); a UniProt-annotated variant site (in rp75); the 'disordered' region

Full AGBL5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AGBL5 p.Ser651Gly Uncertain significance ★ ⚠ same residue
AGBL5 p.Ser651= Likely benign ★ same residue
AGBL5 c.2090-2dup Uncertain significance ★★ same type
AGBL5 c.216-14dup Likely benign ★★ same type
AGBL5 c.552-9dup Benign/Likely benign ★★ same type
AGBL5 p.Ala428fs Pathogenic ★ same type
AGBL5 p.Arg549fs Pathogenic ★ same type
AGBL5 p.Asn625fs Pathogenic ★ 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/agbl5-p-ser651ter (accessed [today's date]).

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