Is APBB1 p.Arg506Gln (c.1517G>A) pathogenic?

APBB1 p.Arg506Gln (c.1517G>A) is classified Uncertain significance in APBB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-20). AlphaMissense: likely benign (0.2752); Very rare (popmax 0.00668%, afr).

How common is APBB1 p.Arg506Gln (c.1517G>A) in the general population?

APBB1 p.Arg506Gln (c.1517G>A) is very rare (popmax 0.00668%, afr) (gnomAD).

What do computational predictors say about APBB1 p.Arg506Gln (c.1517G>A)?

AlphaMissense predicts likely benign (score 0.2752) — an in-silico prediction, not a clinical call.

APBB1 p.Arg506Gln

c.1517G>A · rs376108082 · VCV3127662

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2752 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2752	likely benign
REVEL	0.375	indeterminate
SaProt	LLR -10.86	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.3, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 15 kb · p 2.6e-06 · regional, not allelic
Overall
CADD	27.7	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 0.00668% African / African-American · 5/74,876 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.00124% 20/1,613,834 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00668%	14,975
East Asian	0.00223%	44,874
Remaining individualsnot grpmax-eligible	0.0016%	62,478
South Asian	0.0011%	91,066
European (non-Finnish)	0.00102%	98,328

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: APBB1
Protein: p.Arg506Gln
Coding: c.1517G>A
MANE Select: NM_001164
dbSNP: rs376108082
Type: single nucleotide variant
Location: chr11:6401416 (GRCh38)
Gene constraint: LOEUF 0.401 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 60.75 · 11 PDB
Residue 506: the pid 1 domain

Full APBB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APBB1 p.Arg506Trp Uncertain significance ★ ⚠ same residue
SMPD1 p.Arg498Leu Pathogenic ★★ same type
APBB1 p.Ala371= Benign ★★ same type
APBB1 p.Arg51Cys Benign ★★ ⚠ same type
APBB1 p.Asn126= Benign ★★ same type
APBB1 p.Leu385= Benign ★★ same type
APBB1 p.Met327Val Likely benign ★★ same type
APBB1 c.721+1G>T 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/apbb1-p-arg506gln (accessed [today's date]).

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