Is APOA5 p.Ser3Asn (c.8G>A) pathogenic?

APOA5 p.Ser3Asn (c.8G>A) is classified Uncertain significance in APOA5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-17). AlphaMissense: likely benign (0.1264); Very rare (popmax 0.00223%, eas).

How common is APOA5 p.Ser3Asn (c.8G>A) in the general population?

APOA5 p.Ser3Asn (c.8G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about APOA5 p.Ser3Asn (c.8G>A)?

AlphaMissense predicts likely benign (score 0.1264) — an in-silico prediction, not a clinical call.

APOA5 p.Ser3Asn

c.8G>A · rs1183005271 · VCV2683167

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1264 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1264	likely benign
REVEL	0.104	moderately benign-leaning
SaProt	LLR -7.31	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 -0.38	GERP 0.37
Regional constraint	o/e 0.92	unconstrained · MANE · 1,729 bp · p 0.086 · regional, not allelic
Overall
CADD	9.625	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 0.00223% East Asian · 1/44,880 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000434% 7/1,614,192 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,880
Finnishnot grpmax-eligible	0.00156%	64,020
European (non-Finnish)	0.000424%	236,005

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: APOA5
Protein: p.Ser3Asn
Coding: c.8G>A
MANE Select: NM_001371904
dbSNP: rs1183005271
Type: single nucleotide variant
Location: chr11:116791853 (GRCh38)
Gene constraint: LOEUF 1.146 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.38

Full APOA5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APOA5 p.Gln97Ter Pathogenic ★★ same type
APOA5 c.161+3G>A Uncertain significance ★★ same type
APOA5 c.161+5G>C Uncertain significance ★★ same type
APOA5 p.Ala105Ser Uncertain significance ★★ ⚠ same type
APOA5 p.Ala244Ser Uncertain significance ★★ ⚠ same type
APOA5 p.Ala302Val Uncertain significance ★★ ⚠ same type
APOA5 p.Ala82Val Uncertain significance ★★ ⚠ same type
APOA5 p.Arg143His 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/apoa5-p-ser3asn (accessed [today's date]).

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