Is ABCA7 p.Val1599Met (c.4795G>A) pathogenic?

ABCA7 p.Val1599Met (c.4795G>A) is classified Likely benign in ABCA7 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-05-01). AlphaMissense: likely benign (0.2142); Low-frequency (popmax 1.65%, mid).

How common is ABCA7 p.Val1599Met (c.4795G>A) in the general population?

ABCA7 p.Val1599Met (c.4795G>A) is low-frequency (popmax 1.65%, mid) (gnomAD).

What do computational predictors say about ABCA7 p.Val1599Met (c.4795G>A)?

AlphaMissense predicts likely benign (score 0.2142) — an in-silico prediction, not a clinical call.

ABCA7 p.Val1599Met

c.4795G>A · rs117187003 · VCV493242

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.2142 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.65%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2142	likely benign
REVEL	0.576	indeterminate
SaProt	LLR -8.12	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 5.1	GERP -3.2, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 24 kb · p 5.6e-14 · regional, not allelic
Overall
CADD	26.4	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 1.65% Middle Eastern · 100/6,062 alleles

Filtering AF 1.39% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.29%

Overall 0.334% 5,397/1,613,914 alleles · low-frequency

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	10.2%	10
Middle Easterngrpmax	1.65%	61
Finnishnot grpmax-eligible	0.796%	126
European (non-Finnish)	0.349%	286
Ashkenazi Jewishnot grpmax-eligible	0.304%	329
Admixed American	0.288%	347
Remaining individualsnot grpmax-eligible	0.27%	370
South Asian	0.108%	929
African / African-American	0.0573%	1,745

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val1599Met
Coding: c.4795G>A
MANE Select: NM_019112
dbSNP: rs117187003
Type: single nucleotide variant
Location: chr19:1057344 (GRCh38)
Gene constraint: LOEUF 1.368 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.77 · 6 PDB
Residue 1599: an α-helix

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

Similar variants

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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-val1599met (accessed [today's date]).

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