Is ABCA7 p.Asp871His (c.2611G>C) pathogenic?

ABCA7 p.Asp871His (c.2611G>C) is classified Uncertain significance in ABCA7 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-02-11). AlphaMissense: likely benign (0.3269); Rare (popmax 0.371%, afr).

How common is ABCA7 p.Asp871His (c.2611G>C) in the general population?

ABCA7 p.Asp871His (c.2611G>C) is rare (popmax 0.371%, afr) (gnomAD).

What do computational predictors say about ABCA7 p.Asp871His (c.2611G>C)?

AlphaMissense predicts likely benign (score 0.3269) — an in-silico prediction, not a clinical call.

ABCA7 p.Asp871His

c.2611G>C · rs139251928 · VCV3048450

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3269 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.371%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3269	likely benign
REVEL	0.628	indeterminate
SaProt	LLR -11.76	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP -0.64, phastCons 0.94
Regional constraint	o/e 1.14	unconstrained · MANE · 24 kb · p 5.6e-14 · regional, not allelic
Overall
CADD	19.93	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 0.371% African / African-American · 278/74,998 alleles

Filtering AF 0.335% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.321%

Overall 0.0221% 357/1,612,188 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.371%	270
Middle Eastern	0.264%	378
Remaining individualsnot grpmax-eligible	0.0416%	2,402
Admixed American	0.03%	3,332
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,794
European (non-Finnish)	0.00144%	69,396

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.Asp871His
Coding: c.2611G>C
MANE Select: NM_019112
dbSNP: rs139251928
Type: single nucleotide variant
Location: chr19:1050979 (GRCh38)
Gene constraint: LOEUF 1.368 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.77 · 6 PDB
Residue 871: the abc transporter 1 domain

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

Similar variants

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
ABCA7 p.Gln925Ter 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-asp871his (accessed [today's date]).

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