Is APBA1 p.Ala506Pro (c.1516G>C) pathogenic?

APBA1 p.Ala506Pro (c.1516G>C) is classified Uncertain significance in APBA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-10). AlphaMissense: likely benign (0.3129); Very rare (popmax 0.00167%, amr).

How common is APBA1 p.Ala506Pro (c.1516G>C) in the general population?

APBA1 p.Ala506Pro (c.1516G>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about APBA1 p.Ala506Pro (c.1516G>C)?

AlphaMissense predicts likely benign (score 0.3129) — an in-silico prediction, not a clinical call.

APBA1 p.Ala506Pro

c.1516G>C · VCV3924277

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3129 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3129	likely benign
REVEL	0.215	benign-leaning
SaProt	LLR -7.26	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 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 15 kb · p 3e-05 · regional, not allelic
Overall
CADD	28.9	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 0.00167% Admixed American · 1/60,008 alleles

Overall 6.84e-05% 1/1,461,438 alleles · very rare

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: APBA1
Protein: p.Ala506Pro
Coding: c.1516G>C
MANE Select: NM_001163
Type: single nucleotide variant
Location: chr9:69457139 (GRCh38)
Gene constraint: LOEUF 0.978 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.85 · 8 PDB
Residue 506: the pid domain

Full APBA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APBA1 p.Asn810Ser Uncertain significance ★★ ⚠ same type
APBA1 p.Ala225Val Uncertain significance ★ ⚠ same type
APBA1 p.Ala329Val Uncertain significance ★ ⚠ same type
APBA1 p.Ala345Thr Uncertain significance ★ ⚠ same type
APBA1 p.Ala574Val Uncertain significance ★ ⚠ same type
APBA1 p.Arg143Cys Uncertain significance ★ ⚠ same type
APBA1 p.Arg177His Uncertain significance ★ ⚠ same type
APBA1 p.Arg210Gly 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/apba1-p-ala506pro (accessed [today's date]).

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