Is AP5B1 p.Arg155Ter (c.463C>T) pathogenic?

AP5B1 p.Arg155Ter (c.463C>T) is classified Likely pathogenic in AP5B1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-17). Very rare (popmax 0.00353%, sas); Associated with Macular dystrophy with or without extraocular features.

What condition is associated with AP5B1 p.Arg155Ter (c.463C>T)?

AP5B1 p.Arg155Ter (c.463C>T) is associated with Macular dystrophy with or without extraocular features (ClinVar).

How common is AP5B1 p.Arg155Ter (c.463C>T) in the general population?

AP5B1 p.Arg155Ter (c.463C>T) is very rare (popmax 0.00353%, sas) (gnomAD).

AP5B1 p.Arg155Ter

c.463C>T · VCV3777719

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00353%, sas)

Conditions

Macular dystrophy with or without extraocular features

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	escapes	premature termination codon in the last exon (2 of 2) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 1.7, phastCons 1
Overall
CADD	38.0	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 0.00353% South Asian · 3/84,966 alleles

Filtering AF 0.000938% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00046%

Overall 0.000214% 3/1,402,302 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: AP5B1
Protein: p.Arg155Ter
Coding: c.463C>T
MANE Select: NM_138368
Type: single nucleotide variant
Location: chr11:65780030 (GRCh38)
Gene constraint: LOEUF 1.424 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.29 · 2 PDB
Residue 155: an α-helix

Full AP5B1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Macular dystrophy with or without extraocular features

Similar variants

AP5B1 p.Arg731Ter Pathogenic/Likely pathogenic ★★ same condition
AP5B1 p.Arg857Trp Uncertain significance ★★ ⚠ same condition
AP5B1 p.Leu544Pro Likely pathogenic ★ same condition
AP5B1 p.Leu785Pro Conflicting classifications of pathogenicity ★ ⚠ same condition
AP5B1 p.Arg298fs Likely pathogenic ★ same condition
AP5B1 p.Gln288fs Likely pathogenic ★ same condition
AP5B1 p.Leu104fs Likely pathogenic ★ same condition
AP5B1 p.Leu401Phe 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/ap5b1-p-arg155ter (accessed [today's date]).

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