Is AP4B1 p.Phe311= (c.933T>C) pathogenic?

AP4B1 p.Phe311= (c.933T>C) is classified Likely benign in AP4B1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-05-20). Ultra-rare (popmax 0.0626%, sas); Associated with Inborn genetic diseases.

What condition is associated with AP4B1 p.Phe311= (c.933T>C)?

AP4B1 p.Phe311= (c.933T>C) is associated with Inborn genetic diseases (ClinVar).

How common is AP4B1 p.Phe311= (c.933T>C) in the general population?

AP4B1 p.Phe311= (c.933T>C) is ultra-rare (popmax 0.0626%, sas) (gnomAD).

AP4B1 p.Phe311=

c.933T>C · rs576006432 · VCV1766632

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0626%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.67	GERP -4.3
Overall
CADD	10.69	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0626% South Asian · 57/91,086 alleles

Filtering AF 0.0496% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0449%

Overall 0.00365% 59/1,614,250 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0626%	1,598
Remaining individualsnot grpmax-eligible	0.0032%	31,256

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: AP4B1
Protein: p.Phe311=
Coding: c.933T>C
MANE Select: NM_001253852
dbSNP: rs576006432
Type: single nucleotide variant
Location: chr1:113900085 (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

Disease context

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

Similar variants

AP4B1 c.114-2A>G Pathogenic ★★ same condition
AP4B1 c.470-6T>G Uncertain significance ★★ same condition
AP4B1 p.Ala361Val Uncertain significance ★★ ⚠ same condition
AP4B1 p.Ala83Pro Uncertain significance ★★ ⚠ same condition
AP4B1 p.Arg130Gln Uncertain significance ★★ ⚠ same condition
AP4B1 p.Arg169His Uncertain significance ★★ ⚠ same condition
AP4B1 p.Arg224Cys Uncertain significance ★★ ⚠ same condition
AP4B1 p.Arg301His 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/ap4b1-p-phe311 (accessed [today's date]).

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