Is AP4B1 p.Val194= (c.582C>G) pathogenic?

AP4B1 p.Val194= (c.582C>G) is classified Likely benign in AP4B1 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-09-15). Absent from gnomAD v4.1.

How common is AP4B1 p.Val194= (c.582C>G) in the general population?

AP4B1 p.Val194= (c.582C>G) is absent from gnomAD v4.1 (gnomAD).

AP4B1 p.Val194=

c.582C>G · rs1571569664 · VCV711010

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.7	GERP 1.3, phastCons 1
Overall
CADD	8.869	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AP4B1
Protein: p.Val194=
Coding: c.582C>G
MANE Select: NM_001253852
dbSNP: rs1571569664
Type: single nucleotide variant
Location: chr1:113901271 (GRCh38)
Gene constraint: LOEUF 0.777 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.56 · 5 PDB

Full AP4B1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AP4B1 p.Val194Ala Uncertain significance ★ ⚠ same residue
AP4B1 p.Val194Leu Uncertain significance ★ ⚠ same residue
AP4B1 p.Val194del Uncertain significance ★ same residue
AP4B1 c.114-2A>C Pathogenic ★★ same type
AP4B1 c.114-2A>G Pathogenic ★★ same type
AP4B1 p.Arg102Ter Pathogenic ★★ same type
AP4B1 p.Arg206Ter Pathogenic/Likely pathogenic ★★ same type
AP4B1 p.Arg353Ter Pathogenic/Likely 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/ap4b1-p-val194 (accessed [today's date]).

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