Is ABCA7 p.Pro152Leu (c.455C>T) pathogenic?

ABCA7 p.Pro152Leu (c.455C>T) is classified Benign/Likely benign in ABCA7 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-10-22). AlphaMissense: likely benign (0.0967); Low-frequency (popmax 1.4%, afr).

How common is ABCA7 p.Pro152Leu (c.455C>T) in the general population?

ABCA7 p.Pro152Leu (c.455C>T) is low-frequency (popmax 1.4%, afr) (gnomAD).

What do computational predictors say about ABCA7 p.Pro152Leu (c.455C>T)?

AlphaMissense predicts likely benign (score 0.0967) — an in-silico prediction, not a clinical call.

ABCA7 p.Pro152Leu

c.455C>T · rs151054304 · VCV777342

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0967 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.4%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0967	likely benign
REVEL	0.133	moderately benign-leaning
SaProt	LLR -5.34	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 0.12	GERP 1.2
Regional constraint	o/e 1.14	unconstrained · MANE · 24 kb · p 5.6e-14 · regional, not allelic
Overall
CADD	0.581	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 1.4% African / African-American · 1,049/74,872 alleles

Filtering AF 1.33% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.3%

Overall 0.0739% 1,183/1,599,772 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.4%	71
Remaining individualsnot grpmax-eligible	0.108%	923
Admixed American	0.084%	1,191
Middle Eastern	0.0333%	3,002
European (non-Finnish)	0.0012%	83,599
South Asian	0.00111%	89,838

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.Pro152Leu
Coding: c.455C>T
MANE Select: NM_019112
dbSNP: rs151054304
Type: single nucleotide variant
Location: chr19:1042354 (GRCh38)
Gene constraint: LOEUF 1.368 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.77 · 6 PDB
Residue 152: a disulfide bond

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
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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-pro152leu (accessed [today's date]).

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