Is ABCA7 p.Arg2056Ser (c.6166C>A) pathogenic?

ABCA7 p.Arg2056Ser (c.6166C>A) is classified Uncertain significance in ABCA7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-16). AlphaMissense: likely benign (0.3182); Rare (popmax 0.117%, sas).

How common is ABCA7 p.Arg2056Ser (c.6166C>A) in the general population?

ABCA7 p.Arg2056Ser (c.6166C>A) is rare (popmax 0.117%, sas) (gnomAD).

What do computational predictors say about ABCA7 p.Arg2056Ser (c.6166C>A)?

AlphaMissense predicts likely benign (score 0.3182) — an in-silico prediction, not a clinical call.

ABCA7 p.Arg2056Ser

c.6166C>A · rs372768841 · VCV2590330

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3182 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.117%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3182	likely benign
REVEL	0.424	indeterminate
SaProt	LLR -7.24	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.46 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.036	GERP 0.022, phastCons 0.23
Regional constraint	o/e 1.14	unconstrained · MANE · 24 kb · p 5.6e-14 · regional, not allelic
Overall
CADD	20.7	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 0.117% South Asian · 100/85,704 alleles

Filtering AF 0.0981% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0912%

Overall 0.0075% 117/1,559,532 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.117%	857
African / African-American	0.00953%	10,495
Admixed American	0.00945%	10,577
Remaining individualsnot grpmax-eligible	0.00662%	15,099
European (non-Finnish)	8.67e-05%	1,153,794

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.Arg2056Ser
Coding: c.6166C>A
MANE Select: NM_019112
dbSNP: rs372768841
Type: single nucleotide variant
Location: chr19:1065052 (GRCh38)
Gene constraint: LOEUF 1.368 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.77 · 6 PDB
Residue 2056: a β-strand

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

Similar variants

ABCA7 p.Arg2056His Uncertain significance ★ ⚠ same residue
ABCA7 c.2684+5G>A Uncertain significance ★★ same type
ABCA7 c.3578-2A>G Uncertain significance ★★ same type
ABCA7 p.Arg1026Cys Uncertain significance ★★ ⚠ same type
ABCA7 p.Arg652Cys Uncertain significance ★★ ⚠ same type
ABCA7 p.Arg880Trp Uncertain significance ★★ ⚠ same type
ABCA7 p.Asp1452Asn Uncertain significance ★★ ⚠ same type
ABCA7 p.Asp2085Asn 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/abca7-p-arg2056ser (accessed [today's date]).

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