Is APOD p.Ala17Glu (c.50C>A) pathogenic?

APOD p.Ala17Glu (c.50C>A) is classified Uncertain significance in APOD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-18). AlphaMissense: likely benign (0.2231); Ultra-rare (popmax 0.015%, amr).

How common is APOD p.Ala17Glu (c.50C>A) in the general population?

APOD p.Ala17Glu (c.50C>A) is ultra-rare (popmax 0.015%, amr) (gnomAD).

What do computational predictors say about APOD p.Ala17Glu (c.50C>A)?

AlphaMissense predicts likely benign (score 0.2231) — an in-silico prediction, not a clinical call.

APOD p.Ala17Glu

c.50C>A · VCV3934611

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2231 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2231	likely benign
REVEL	0.221	benign-leaning
SaProt	LLR -8.24	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 -0.35	GERP -3.4
Regional constraint	o/e 0.97	unconstrained · MANE · 11 kb · p 0.66 · regional, not allelic
Overall
CADD	0.124	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 0.015% Admixed American · 9/60,008 alleles

Filtering AF 0.00773% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00578%

Overall 0.000682% 11/1,613,904 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.015%	6,668
Remaining individualsnot grpmax-eligible	0.0016%	62,482
European (non-Finnish)	8.47e-05%	1,180,006

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: APOD
Protein: p.Ala17Glu
Coding: c.50C>A
MANE Select: NM_001647
Type: single nucleotide variant
Location: chr3:195579412 (GRCh38)
Gene constraint: LOEUF 1.436 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.57 · 2 PDB

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

Similar variants

APOD p.Phe15Ser Benign ★★ same type
APOD p.Ala146Thr Uncertain significance ★ ⚠ same type
APOD p.Arg60Cys Uncertain significance ★ ⚠ same type
APOD p.Asp124Asn Uncertain significance ★ ⚠ same type
APOD p.Gln139Glu Uncertain significance ★ ⚠ same type
APOD p.Gln34Arg Uncertain significance ★ ⚠ same type
APOD p.Gln79Glu Uncertain significance ★ ⚠ same type
APOD p.Glu48Lys 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/apod-p-ala17glu (accessed [today's date]).

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