Is APOC2 p.Tyr59= (c.177C>T) pathogenic?

APOC2 p.Tyr59= (c.177C>T) is classified Likely benign in APOC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-08-06). Very rare (popmax 0.0022%, sas); Associated with Cardiovascular phenotype.

What condition is associated with APOC2 p.Tyr59= (c.177C>T)?

APOC2 p.Tyr59= (c.177C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is APOC2 p.Tyr59= (c.177C>T) in the general population?

APOC2 p.Tyr59= (c.177C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

APOC2 p.Tyr59=

c.177C>T · rs120074111 · VCV1779944

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP -4.5	GERP -1.6
Overall
CADD	5.897	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,092 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.00118% 19/1,613,844 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,546
Remaining individualsnot grpmax-eligible	0.0016%	62,484
Finnishnot grpmax-eligible	0.00157%	63,808
European (non-Finnish)	0.00127%	78,669

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: APOC2
Protein: p.Tyr59=
Coding: c.177C>T
MANE Select: NM_000483
dbSNP: rs120074111
Type: single nucleotide variant
Location: chr19:44948822 (GRCh38)
Gene constraint: LOEUF 1.054 · pLI 0.07 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.81 · 4 PDB
Residue 59: an α-helix

Full APOC2 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

APOC2 p.Gln25Ter Likely pathogenic ★★ same condition
APOC2 p.Ala54Asp Uncertain significance ★★ ⚠ same condition
APOC2 p.Ala55Thr Uncertain significance ★★ ⚠ same condition
APOC2 p.Ser76Ile Uncertain significance ★★ ⚠ same condition
APOC2 p.Thr23Ile Uncertain significance ★★ ⚠ same condition
APOC2 p.Thr86Arg Uncertain significance ★★ ⚠ same condition
APOC2 p.Val67Ile Uncertain significance ★★ ⚠ same condition
APOC2 c.56-4G>C 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/apoc2-p-tyr59 (accessed [today's date]).

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