Is APOE p.Val213= (c.639G>T) pathogenic?

APOE p.Val213= (c.639G>T) is classified Likely benign in APOE (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-09-05). Ultra-rare (popmax 0.0341%, amr); Associated with Cardiovascular phenotype.

What condition is associated with APOE p.Val213= (c.639G>T)?

APOE p.Val213= (c.639G>T) is associated with Cardiovascular phenotype (ClinVar).

How common is APOE p.Val213= (c.639G>T) in the general population?

APOE p.Val213= (c.639G>T) is ultra-rare (popmax 0.0341%, amr) (gnomAD).

APOE p.Val213=

c.639G>T · rs1313313298 · VCV718465

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0341%, amr)

Conditions

Cardiovascular phenotype

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 -0.26	GERP -2.5
Overall
CADD	2.514	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0341% Admixed American · 16/46,942 alleles

Filtering AF 0.0213% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0173%

Overall 0.00113% 17/1,503,900 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0341%	2,934
Remaining individualsnot grpmax-eligible	0.00171%	58,370

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.Val213=
Coding: c.639G>T
MANE Select: NM_000041
dbSNP: rs1313313298
Type: single nucleotide variant
Location: chr19:44908935 (GRCh38)
Gene constraint: LOEUF 1.319 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.13 · 31 PDB
Residue 213: the '8 x 22 aa approximate tandem repeats' region; the 'lipid-binding and lipoprotein association' region; an α-helix

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

APOE p.Val213Gly Uncertain significance ★★ ⚠ same residue
APOE p.Arg43Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
APOE p.Arg246Pro Uncertain significance ★★ same condition
APOE p.Arg56His Uncertain significance ★★ ⚠ same condition
APOE p.Gln119Pro Uncertain significance ★★ same condition
APOE p.Gln181His Uncertain significance ★★ ⚠ same condition
APOE p.Ser112Tyr Uncertain significance ★★ ⚠ same condition
APOE p.Trp294Cys Uncertain significance ★★ ⚠ 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-val213 (accessed [today's date]).

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