Is ABCA7 p.Leu33Pro (c.98T>C) pathogenic?

ABCA7 p.Leu33Pro (c.98T>C) is classified Likely benign in ABCA7 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-02-16). AlphaMissense: likely pathogenic (0.6505); Rare (popmax 0.1%, amr).

How common is ABCA7 p.Leu33Pro (c.98T>C) in the general population?

ABCA7 p.Leu33Pro (c.98T>C) is rare (popmax 0.1%, amr) (gnomAD).

What do computational predictors say about ABCA7 p.Leu33Pro (c.98T>C)?

AlphaMissense predicts likely pathogenic (score 0.6505) — an in-silico prediction, not a clinical call.

ABCA7 p.Leu33Pro

c.98T>C · rs764096823 · VCV715315

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6505 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.1%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6505	likely pathogenic
REVEL	0.902	moderately pathogenic-leaning
SaProt	LLR -8.67	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 24 kb · p 5.6e-14 · regional, not allelic
Overall
CADD	26.0	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 0.1% Admixed American · 60/59,996 alleles

Filtering AF 0.0798% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0724%

Overall 0.00378% 61/1,613,442 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.1%	1,000
Remaining individualsnot grpmax-eligible	0.0016%	62,480

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.Leu33Pro
Coding: c.98T>C
MANE Select: NM_019112
dbSNP: rs764096823
Type: single nucleotide variant
Location: chr19:1041541 (GRCh38)
Gene constraint: LOEUF 1.368 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.77 · 6 PDB
Residue 33: an α-helix

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-leu33pro (accessed [today's date]).

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