Is APOE p.Val129= (c.387G>A) pathogenic?

APOE p.Val129= (c.387G>A) is classified Likely benign in APOE (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-10-14). Very rare (popmax 0.0019%, amr); Associated with APOE-related disorder.

What condition is associated with APOE p.Val129= (c.387G>A)?

APOE p.Val129= (c.387G>A) is associated with APOE-related disorder (ClinVar).

How common is APOE p.Val129= (c.387G>A) in the general population?

APOE p.Val129= (c.387G>A) is very rare (popmax 0.0019%, amr) (gnomAD).

APOE p.Val129=

c.387G>A · rs1056815951 · VCV3032874

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0019%, amr)

Conditions

APOE-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -0.53, phastCons 1
Overall
CADD	6.156	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0019% Admixed American · 1/52,732 alleles

Filtering AF 6.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000318% 5/1,570,028 alleles · very rare exomes 4/1,417,834 · genomes 1/152,194 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0019%	52,732
Remaining individualsnot grpmax-eligible	0.00164%	60,832
European (non-Finnish)	0.000259%	386,087

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: APOE
Protein: p.Val129=
Coding: c.387G>A
MANE Select: NM_000041
dbSNP: rs1056815951
Type: single nucleotide variant
Location: chr19:44908683 (GRCh38)
Gene constraint: LOEUF 1.319 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.13 · 31 PDB
Residue 129: the '8 x 22 aa approximate tandem repeats' region; an α-helix

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

Disease context

APOE-related disorder

Similar variants

APOE c.-24+47G>A Uncertain significance ★ same condition
APOE p.Arg152Gln Pathogenic ⚠ same condition
APOE p.Arg246Cys Pathogenic ⚠ same condition
APOE p.Arg292His Pathogenic ⚠ same condition
APOE p.Glu21Lys Pathogenic ⚠ same condition
APOE c.237-8G>C Likely benign same condition
APOE c.*5C>T Likely benign same condition
APOE p.Arg165= Likely benign same condition

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/apoe-p-val129 (accessed [today's date]).

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