Is APOD p.Pro53Ser (c.157C>T) pathogenic?

APOD p.Pro53Ser (c.157C>T) is classified Uncertain significance in APOD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-24). AlphaMissense: ambiguous (0.4228); Very rare (popmax 0.0011%, sas).

How common is APOD p.Pro53Ser (c.157C>T) in the general population?

APOD p.Pro53Ser (c.157C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about APOD p.Pro53Ser (c.157C>T)?

AlphaMissense predicts ambiguous (score 0.4228) — an in-silico prediction, not a clinical call.

APOD p.Pro53Ser

c.157C>T · VCV3417688

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4228 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Computational evidence

Protein change
AlphaMissense	0.4228	ambiguous
REVEL	0.412	indeterminate
SaProt	LLR -7.28	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 11 kb · p 0.66 · regional, not allelic
Overall
CADD	25.1	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 0.0011% South Asian · 1/91,070 alleles

Overall 6.84e-05% 1/1,461,858 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: APOD
Protein: p.Pro53Ser
Coding: c.157C>T
MANE Select: NM_001647
Type: single nucleotide variant
Location: chr3:195573938 (GRCh38)
Gene constraint: LOEUF 1.436 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.57 · 2 PDB
Residue 53: a disulfide bond

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.Ala17Glu 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

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-pro53ser (accessed [today's date]).

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