Is APPBP2 p.Arg545Gln (c.1634G>A) pathogenic?

APPBP2 p.Arg545Gln (c.1634G>A) is classified Uncertain significance in APPBP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-17). AlphaMissense: likely benign (0.0857); Ultra-rare (popmax 0.0122%, nfe).

How common is APPBP2 p.Arg545Gln (c.1634G>A) in the general population?

APPBP2 p.Arg545Gln (c.1634G>A) is ultra-rare (popmax 0.0122%, nfe) (gnomAD).

What do computational predictors say about APPBP2 p.Arg545Gln (c.1634G>A)?

AlphaMissense predicts likely benign (score 0.0857) — an in-silico prediction, not a clinical call.

APPBP2 p.Arg545Gln

c.1634G>A · rs377108787 · VCV2204909

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0857 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0122%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0857	likely benign
REVEL	0.504	indeterminate
SaProt	LLR -6.08	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 189 bp · p 0.019 · regional, not allelic
Overall
CADD	23.6	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 0.0122% European (non-Finnish) · 144/1,180,036 alleles

Filtering AF 0.0105% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00994%

Overall 0.00967% 156/1,613,972 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0122%	8,195
Admixed American	0.00833%	11,998
South Asian	0.00549%	18,218
Remaining individualsnot grpmax-eligible	0.0016%	62,484
African / African-American	0.00133%	74,908

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: APPBP2
Protein: p.Arg545Gln
Coding: c.1634G>A
MANE Select: NM_006380
dbSNP: rs377108787
Type: single nucleotide variant
Location: chr17:60447705 (GRCh38)
Gene constraint: LOEUF 0.34 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 93.52 · 6 PDB
Residue 545: an α-helix

Full APPBP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APPBP2 p.Ala272Gly Uncertain significance ★ ⚠ same type
APPBP2 p.Arg161Cys Uncertain significance ★ ⚠ same type
APPBP2 p.Arg27His Uncertain significance ★ ⚠ same type
APPBP2 p.Arg71Thr Uncertain significance ★ ⚠ same type
APPBP2 p.Asn24Ser Uncertain significance ★ ⚠ same type
APPBP2 p.Asp154Asn Uncertain significance ★ ⚠ same type
APPBP2 p.Gln487His Uncertain significance ★ ⚠ same type
APPBP2 p.Gln565His 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/appbp2-p-arg545gln (accessed [today's date]).

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