Is AOPEP p.Arg767Ser (c.2301G>T) pathogenic?

AOPEP p.Arg767Ser (c.2301G>T) is classified Uncertain significance in AOPEP (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-30). AlphaMissense: likely benign (0.1593); Very rare (popmax 8.48e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with AOPEP p.Arg767Ser (c.2301G>T)?

AOPEP p.Arg767Ser (c.2301G>T) is associated with Inborn genetic diseases (ClinVar).

How common is AOPEP p.Arg767Ser (c.2301G>T) in the general population?

AOPEP p.Arg767Ser (c.2301G>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about AOPEP p.Arg767Ser (c.2301G>T)?

AlphaMissense predicts likely benign (score 0.1593) — an in-silico prediction, not a clinical call.

AOPEP p.Arg767Ser

c.2301G>T · rs939421378 · VCV3127405

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1593 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1593	likely benign
REVEL	0.107	moderately benign-leaning
SaProt	LLR -6.53	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 -2.2	GERP -5.2
Regional constraint	o/e 1.03	unconstrained · MANE · 282 kb · p 0.54 · regional, not allelic
Overall
CADD	0.041	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 8.48e-05% European (non-Finnish) · 1/1,179,822 alleles

Overall 0.000657% 1/152,156 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: AOPEP
Protein: p.Arg767Ser
Coding: c.2301G>T
MANE Select: NM_001193329
dbSNP: rs939421378
Type: single nucleotide variant
Location: chr9:95080762 (GRCh38)
Gene constraint: LOEUF 0.979 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.36
Residue 767: a UniProt-annotated variant site (in dyt31)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AOPEP p.Arg767Lys Uncertain significance ★ ⚠ same residue
AOPEP p.Arg665Cys Uncertain significance ★ ⚠ same condition
AOPEP p.Arg801Trp Uncertain significance ★ ⚠ same condition
AOPEP p.His116Arg Uncertain significance ★ ⚠ same condition
AOPEP p.Ile43Val Uncertain significance ★ ⚠ same condition
AOPEP p.Leu673Phe Uncertain significance ★ ⚠ same condition
AOPEP p.Lys579Arg Uncertain significance ★ ⚠ same condition
AOPEP p.Lys757Arg Uncertain significance ★ ⚠ same condition

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/aopep-p-arg767ser (accessed [today's date]).

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