Is AP4B1 p.Ala200Ser (c.598G>T) pathogenic?

AP4B1 p.Ala200Ser (c.598G>T) is classified Uncertain significance in AP4B1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-03). AlphaMissense: likely benign (0.3162); Very rare (popmax 0.00446%, eas); Associated with Inborn genetic diseases.

What condition is associated with AP4B1 p.Ala200Ser (c.598G>T)?

AP4B1 p.Ala200Ser (c.598G>T) is associated with Inborn genetic diseases (ClinVar).

How common is AP4B1 p.Ala200Ser (c.598G>T) in the general population?

AP4B1 p.Ala200Ser (c.598G>T) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about AP4B1 p.Ala200Ser (c.598G>T)?

AlphaMissense predicts likely benign (score 0.3162) — an in-silico prediction, not a clinical call.

AP4B1 p.Ala200Ser

c.598G>T · rs1371587129 · VCV3127549

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3162 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3162	likely benign
REVEL	0.215	benign-leaning
SaProt	LLR -9.78	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 7.6	GERP 2.2, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 9,649 bp · p 0.84 · regional, not allelic
Overall
CADD	26.0	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 0.00446% East Asian · 2/44,876 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000205% 3/1,461,874 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,438
Remaining individualsnot grpmax-eligible	0.0016%	62,502

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.Ala200Ser
Coding: c.598G>T
MANE Select: NM_001253852
dbSNP: rs1371587129
Type: single nucleotide variant
Location: chr1:113901255 (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-ala200ser (accessed [today's date]).

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