Is APBB1IP p.Pro569Ser (c.1705C>T) pathogenic?

APBB1IP p.Pro569Ser (c.1705C>T) is classified Uncertain significance in APBB1IP (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-15). AlphaMissense: likely benign (0.1353); Very rare (popmax 0.00665%, eas).

How common is APBB1IP p.Pro569Ser (c.1705C>T) in the general population?

APBB1IP p.Pro569Ser (c.1705C>T) is very rare (popmax 0.00665%, eas) (gnomAD).

What do computational predictors say about APBB1IP p.Pro569Ser (c.1705C>T)?

AlphaMissense predicts likely benign (score 0.1353) — an in-silico prediction, not a clinical call.

APBB1IP p.Pro569Ser

c.1705C>T · rs1164039719 · VCV2237679

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1353 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00665%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1353	likely benign
REVEL	0.218	benign-leaning
SaProt	LLR -13.40	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 6.7	GERP 0.4, phastCons 0.99
Regional constraint	o/e 1.08	unconstrained · MANE · 6,746 bp · p 0.12 · regional, not allelic
Overall
CADD	23.8	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 0.00665% East Asian · 2/30,056 alleles

Filtering AF 0.0011% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000412%

Overall 0.000319% 4/1,253,648 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00665%	15,028
Admixed American	0.003%	33,284
African / African-American	0.00153%	65,350

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: APBB1IP
Protein: p.Pro569Ser
Coding: c.1705C>T
MANE Select: NM_019043
dbSNP: rs1164039719
Type: single nucleotide variant
Location: chr10:26567192 (GRCh38)
Gene constraint: LOEUF 0.585 · pLI 0.34 (gnomAD)
Structure: AlphaFold pLDDT 73.37 · 2 PDB
Residue 569: 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-pro569ser (accessed [today's date]).

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