Is ABCA7 p.Arg1237His (c.3710G>A) pathogenic?

ABCA7 p.Arg1237His (c.3710G>A) is classified Benign in ABCA7 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.1021); Low-frequency (popmax 2.62%, afr).

How common is ABCA7 p.Arg1237His (c.3710G>A) in the general population?

ABCA7 p.Arg1237His (c.3710G>A) is low-frequency (popmax 2.62%, afr) (gnomAD).

What do computational predictors say about ABCA7 p.Arg1237His (c.3710G>A)?

AlphaMissense predicts likely benign (score 0.1021) — an in-silico prediction, not a clinical call.

ABCA7 p.Arg1237His

c.3710G>A · rs114614802 · VCV710669

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1021 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.62%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1021	likely benign
REVEL	0.414	indeterminate
SaProt	LLR -9.17	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -3.5, phastCons 0.001
Regional constraint	o/e 1.14	unconstrained · MANE · 24 kb · p 5.6e-14 · regional, not allelic
Overall
CADD	23.5	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 2.62% African / African-American · 1,961/74,932 alleles

Filtering AF 2.52% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.48%

Overall 0.14% 2,234/1,599,996 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.62%	38
Remaining individualsnot grpmax-eligible	0.193%	519
Admixed American	0.139%	720
Middle Eastern	0.0693%	1,443
South Asian	0.0287%	3,490
Finnishnot grpmax-eligible	0.00567%	17,631
European (non-Finnish)	0.00314%	31,851

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.Arg1237His
Coding: c.3710G>A
MANE Select: NM_019112
dbSNP: rs114614802
Type: single nucleotide variant
Location: chr19:1054325 (GRCh38)
Gene constraint: LOEUF 1.368 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.77 · 6 PDB
Residue 1237: a β-strand

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

Similar variants

ABCA7 p.Arg1237= 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-arg1237his (accessed [today's date]).

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