Is APBB1IP p.Asp552His (c.1654G>C) pathogenic?

APBB1IP p.Asp552His (c.1654G>C) is classified Uncertain significance in APBB1IP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-08). AlphaMissense: likely benign (0.1463); Absent from gnomAD v4.1.

How common is APBB1IP p.Asp552His (c.1654G>C) in the general population?

APBB1IP p.Asp552His (c.1654G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about APBB1IP p.Asp552His (c.1654G>C)?

AlphaMissense predicts likely benign (score 0.1463) — an in-silico prediction, not a clinical call.

APBB1IP p.Asp552His

c.1654G>C · rs1837057689 · VCV2545194

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1463 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1463	likely benign
REVEL	0.045	moderately benign-leaning
SaProt	LLR -11.20	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 0.56, phastCons 0.13
Regional constraint	o/e 1.08	unconstrained · MANE · 6,746 bp · p 0.12 · regional, not allelic
Overall
CADD	22.3	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

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: APBB1IP
Protein: p.Asp552His
Coding: c.1654G>C
MANE Select: NM_019043
dbSNP: rs1837057689
Type: single nucleotide variant
Location: chr10:26567141 (GRCh38)
Gene constraint: LOEUF 0.585 · pLI 0.34 (gnomAD)
Structure: AlphaFold pLDDT 73.37 · 2 PDB
Residue 552: the 'disordered' region

Full APBB1IP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APBB1IP p.Ala617Thr Benign ★★ same type
APBB1IP p.Ala622Val Benign ★★ same type
APBB1IP p.Arg429Trp Benign ★★ ⚠ same type
APBB1IP p.Phe208= Benign ★★ same type
APBB1IP p.Ala118Pro Uncertain significance ★ ⚠ same type
APBB1IP p.Ala354Val Uncertain significance ★ ⚠ same type
APBB1IP p.Ala41Thr Uncertain significance ★ ⚠ same type
APBB1IP p.Ala504Val Uncertain significance ★ ⚠ 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/apbb1ip-p-asp552his (accessed [today's date]).

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