Is APOA5 p.Gln207Pro (c.620A>C) pathogenic?

APOA5 p.Gln207Pro (c.620A>C) is classified Uncertain significance in APOA5 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-02-17). AlphaMissense: ambiguous (0.3531); Very rare (popmax 0.00017%, nfe); Associated with dementia.

What condition is associated with APOA5 p.Gln207Pro (c.620A>C)?

APOA5 p.Gln207Pro (c.620A>C) is associated with dementia (ClinVar).

How common is APOA5 p.Gln207Pro (c.620A>C) in the general population?

APOA5 p.Gln207Pro (c.620A>C) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about APOA5 p.Gln207Pro (c.620A>C)?

AlphaMissense predicts ambiguous (score 0.3531) — an in-silico prediction, not a clinical call.

APOA5 p.Gln207Pro

c.620A>C · VCV4075046

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3531 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

dementia

Computational evidence

Protein change
AlphaMissense	0.3531	ambiguous
REVEL	0.721	pathogenic-leaning
SaProt	LLR -11.57	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.68	GERP 3.2, phastCons 0.94
Regional constraint	o/e 0.92	unconstrained · MANE · 1,729 bp · p 0.086 · regional, not allelic
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,594 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,607,410 alleles · very rare

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.Gln207Pro
Coding: c.620A>C
MANE Select: NM_001371904
Type: single nucleotide variant
Location: chr11:116790609 (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

Disease context

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

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-gln207pro (accessed [today's date]).

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