Is AP1B1 p.Ala873Val (c.2618C>T) pathogenic?

AP1B1 p.Ala873Val (c.2618C>T) is classified Likely benign in AP1B1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-04). AlphaMissense: likely benign (0.059); Ultra-rare (popmax 0.0329%, mid); Associated with Inborn genetic diseases.

What condition is associated with AP1B1 p.Ala873Val (c.2618C>T)?

AP1B1 p.Ala873Val (c.2618C>T) is associated with Inborn genetic diseases (ClinVar).

How common is AP1B1 p.Ala873Val (c.2618C>T) in the general population?

AP1B1 p.Ala873Val (c.2618C>T) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about AP1B1 p.Ala873Val (c.2618C>T)?

AlphaMissense predicts likely benign (score 0.059) — an in-silico prediction, not a clinical call.

AP1B1 p.Ala873Val

c.2618C>T · VCV3921911

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.059 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.059	likely benign
REVEL	0.029	moderately benign-leaning
SaProt	LLR -3.99	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 1.3	GERP -2.7, phastCons 0.049
Regional constraint	o/e 0.86	unconstrained · MANE · 13 kb · p 0.0016 · regional, not allelic
Overall
CADD	5.213	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,072 alleles

Filtering AF 0.00885% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00642%

Overall 0.00161% 26/1,609,972 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,036
East Asian	0.0179%	5,596
South Asian	0.0033%	30,341
African / African-American	0.00267%	37,440
Remaining individualsnot grpmax-eligible	0.00161%	62,302
European (non-Finnish)	0.00085%	117,675

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: AP1B1
Protein: p.Ala873Val
Coding: c.2618C>T
MANE Select: NM_001127
Type: single nucleotide variant
Location: chr22:29330526 (GRCh38)
Gene constraint: LOEUF 0.476 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 82.46 · 20 PDB
Residue 873: a UniProt-annotated variant site (in kidar; no protein detected by western blot in patient cells)

Full AP1B1 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

AP1B1 p.Asp234Asn Uncertain significance ★★ ⚠ same condition
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AP1B1 c.2310-3C>G Uncertain significance ★ same condition
AP1B1 p.Ala254Thr Uncertain significance ★ ⚠ same condition
AP1B1 p.Ala352Thr Uncertain significance ★ ⚠ same condition
AP1B1 p.Ala410Thr Uncertain significance ★ ⚠ same condition
AP1B1 p.Ala598Val Uncertain significance ★ ⚠ same condition
AP1B1 p.Ala689Pro 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/ap1b1-p-ala873val (accessed [today's date]).

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