Is AP4S1 p.Phe49fs (c.146_167del) pathogenic?

AP4S1 p.Phe49fs (c.146167del) is classified Pathogenic in AP4S1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-01). Absent from gnomAD.

How common is AP4S1 p.Phe49fs (c.146_167del) in the general population?

AP4S1 p.Phe49fs (c.146_167del) is absent from gnomAD (gnomAD).

AP4S1 p.Phe49fs

c.146_167del · rs2139056017 · VCV1694717

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2.3, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: AP4S1
Protein: p.Phe49fs
Coding: c.146_167del
MANE Select: NM_001128126
dbSNP: rs2139056017
Type: Deletion
Location: chr14:31069850 (GRCh38)
Gene constraint: LOEUF 1.675 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 94.75 · 4 PDB

Full AP4S1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AP4S1 p.Glu34fs Pathogenic ★ same type
AP4S1 c.226_294del Uncertain significance ★ same type
AP4S1 c.306+3006del Conflicting classifications of pathogenicity ★ same type
AP4S1 c.226-172_226-169del Benign ★ same type
AP4S1 c.294+227del Benign ★ same type
AP4S1 c.306+2928_306+2938del Likely benign ★ same type
AP4S1 p.Glu51fs Likely pathogenic same type
AP4S1 c.306+2938del Likely benign 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/ap4s1-p-phe49fs (accessed [today's date]).

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