Is ABCA7 p.Arg571Pro (c.1712G>C) pathogenic?

ABCA7 p.Arg571Pro (c.1712G>C) is classified Uncertain significance in ABCA7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-01). AlphaMissense: likely pathogenic (0.8229); Very rare (popmax 0.00118%, sas).

How common is ABCA7 p.Arg571Pro (c.1712G>C) in the general population?

ABCA7 p.Arg571Pro (c.1712G>C) is very rare (popmax 0.00118%, sas) (gnomAD).

What do computational predictors say about ABCA7 p.Arg571Pro (c.1712G>C)?

AlphaMissense predicts likely pathogenic (score 0.8229) — an in-silico prediction, not a clinical call.

ABCA7 p.Arg571Pro

c.1712G>C · rs757604052 · VCV2648890

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8229 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00118%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8229	likely pathogenic · top 9% in ABCA7
REVEL	0.676	pathogenic-leaning
SaProt	LLR -11.55	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.32	GERP -3.7
Regional constraint	o/e 1.14	unconstrained · MANE · 24 kb · p 5.6e-14 · regional, not allelic
Overall
CADD	22.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00118% South Asian · 1/84,804 alleles

Filtering AF 0.000299% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000216%

Overall 0.00058% 9/1,551,640 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00118%	84,804
European (non-Finnish)	0.000694%	144,124

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: ABCA7
Protein: p.Arg571Pro
Coding: c.1712G>C
MANE Select: NM_019112
dbSNP: rs757604052
Type: single nucleotide variant
Location: chr19:1046891 (GRCh38)
Gene constraint: LOEUF 1.368 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.77 · 6 PDB
Residue 571: an α-helix

Full ABCA7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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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/abca7-p-arg571pro (accessed [today's date]).

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