Is APOC3 p.Ala13Val (c.38C>T) pathogenic?

APOC3 p.Ala13Val (c.38C>T) is classified Uncertain significance in APOC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-27). AlphaMissense: likely benign (0.0987); Ultra-rare (popmax 0.0329%, mid).

How common is APOC3 p.Ala13Val (c.38C>T) in the general population?

APOC3 p.Ala13Val (c.38C>T) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about APOC3 p.Ala13Val (c.38C>T)?

AlphaMissense predicts likely benign (score 0.0987) — an in-silico prediction, not a clinical call.

APOC3 p.Ala13Val

c.38C>T · VCV4800160

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0987 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0987	likely benign
REVEL	0.062	moderately benign-leaning
SaProt	LLR -7.87	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 -3.8	GERP -0.031
Regional constraint	o/e 0.98	unconstrained · MANE · 2,298 bp · p 0.86 · regional, not allelic
Overall
CADD	7.559	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,084 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00241%

Overall 0.00266% 43/1,613,822 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,042
Admixed American	0.00667%	15,002
South Asian	0.00549%	18,217
African / African-American	0.00534%	18,730
Remaining individualsnot grpmax-eligible	0.0048%	20,829
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
European (non-Finnish)	0.00203%	49,167

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: APOC3
Protein: p.Ala13Val
Coding: c.38C>T
MANE Select: NM_000040
Type: single nucleotide variant
Location: chr11:116830620 (GRCh38)
Gene constraint: LOEUF 1.68 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.90 · 1 PDB

Full APOC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APOC3 p.Ala13= Likely benign ★ same residue
APOC3 p.Asp65Asn Uncertain significance ★★ ⚠ same type
APOC3 p.Glu24Lys Uncertain significance ★★ ⚠ same type
APOC3 p.Leu14Phe Uncertain significance ★★ ⚠ same type
APOC3 p.Met36Val Uncertain significance ★★ ⚠ same type
APOC3 p.Val50Met Uncertain significance ★★ ⚠ same type
APOC3 p.Val91Ile Uncertain significance ★★ ⚠ same type
APOC3 c.179+221G>A Benign ★★ 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/apoc3-p-ala13val (accessed [today's date]).

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