Is ABCA7 p.Arg1353Gln (c.4058G>A) pathogenic?

ABCA7 p.Arg1353Gln (c.4058G>A) is classified Uncertain significance in ABCA7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-05). AlphaMissense: likely benign (0.1008); Very rare (popmax 0.00895%, eas).

How common is ABCA7 p.Arg1353Gln (c.4058G>A) in the general population?

ABCA7 p.Arg1353Gln (c.4058G>A) is very rare (popmax 0.00895%, eas) (gnomAD).

What do computational predictors say about ABCA7 p.Arg1353Gln (c.4058G>A)?

AlphaMissense predicts likely benign (score 0.1008) — an in-silico prediction, not a clinical call.

ABCA7 p.Arg1353Gln

c.4058G>A · rs753928366 · VCV3111207

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1008 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00895%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1008	likely benign
REVEL	0.224	benign-leaning
SaProt	LLR -3.42	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 0.24	GERP -3.4
Regional constraint	o/e 1.14	unconstrained · MANE · 24 kb · p 5.6e-14 · regional, not allelic
Overall
CADD	21.4	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 0.00895% East Asian · 4/44,696 alleles

Filtering AF 0.00299% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00181%

Overall 0.00168% 27/1,610,154 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00895%	11,174
Admixed American	0.00502%	19,903
Remaining individualsnot grpmax-eligible	0.00481%	20,781
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,546
African / African-American	0.00134%	74,806
European (non-Finnish)	0.00119%	84,194
South Asian	0.0011%	90,742

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.Arg1353Gln
Coding: c.4058G>A
MANE Select: NM_019112
dbSNP: rs753928366
Type: single nucleotide variant
Location: chr19:1055204 (GRCh38)
Gene constraint: LOEUF 1.368 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.77 · 6 PDB
Residue 1353: a disulfide bond

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-arg1353gln (accessed [today's date]).

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