Is ABCA7 p.Ser2140Thr (c.6419G>C) pathogenic?

ABCA7 p.Ser2140Thr (c.6419G>C) is classified Uncertain significance in ABCA7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-01). AlphaMissense: likely benign (0.0777); Absent from gnomAD v4.1.

How common is ABCA7 p.Ser2140Thr (c.6419G>C) in the general population?

ABCA7 p.Ser2140Thr (c.6419G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCA7 p.Ser2140Thr (c.6419G>C)?

AlphaMissense predicts likely benign (score 0.0777) — an in-silico prediction, not a clinical call.

ABCA7 p.Ser2140Thr

c.6419G>C · rs956276297 · VCV2648898

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0777 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0777	likely benign
REVEL	0.099	moderately benign-leaning
SaProt	LLR -6.80	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 1.1	GERP 1
Regional constraint	o/e 1.14	unconstrained · MANE · 24 kb · p 5.6e-14 · regional, not allelic
Overall
CADD	12.95	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABCA7
Protein: p.Ser2140Thr
Coding: c.6419G>C
MANE Select: NM_019112
dbSNP: rs956276297
Type: single nucleotide variant
Location: chr19:1065403 (GRCh38)
Gene constraint: LOEUF 1.368 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.77 · 6 PDB
Residue 2140: the 'disordered' region

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-ser2140thr (accessed [today's date]).

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