Is APOD p.Tyr128Cys (c.383A>G) pathogenic?

APOD p.Tyr128Cys (c.383A>G) is classified Likely benign in APOD (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-07-27). AlphaMissense: likely pathogenic (0.6165); Rare (popmax 0.645%, afr); Associated with APOD-related disorder.

What condition is associated with APOD p.Tyr128Cys (c.383A>G)?

APOD p.Tyr128Cys (c.383A>G) is associated with APOD-related disorder (ClinVar).

How common is APOD p.Tyr128Cys (c.383A>G) in the general population?

APOD p.Tyr128Cys (c.383A>G) is rare (popmax 0.645%, afr) (gnomAD).

What do computational predictors say about APOD p.Tyr128Cys (c.383A>G)?

AlphaMissense predicts likely pathogenic (score 0.6165) — an in-silico prediction, not a clinical call.

APOD p.Tyr128Cys

c.383A>G · rs150664052 · VCV3038449

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6165 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.645%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

APOD-related disorder

Computational evidence

Protein change
AlphaMissense	0.6165	likely pathogenic
REVEL	0.426	indeterminate
SaProt	LLR -11.59	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 1.8, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 11 kb · p 0.66 · regional, not allelic
Overall
CADD	28.1	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 0.645% African / African-American · 484/75,032 alleles

Filtering AF 0.598% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.579%

Overall 0.0325% 524/1,614,168 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.645%	155
Admixed American	0.035%	2,858
Remaining individualsnot grpmax-eligible	0.0256%	3,907
Middle Eastern	0.0165%	6,062
European (non-Finnish)	0.000169%	590,009

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.Tyr128Cys
Coding: c.383A>G
MANE Select: NM_001647
dbSNP: rs150664052
Type: single nucleotide variant
Location: chr3:195569087 (GRCh38)
Gene constraint: LOEUF 1.436 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.57 · 2 PDB
Residue 128: a β-strand; a disulfide bond

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

Disease context

APOD-related disorder

Similar variants

APOD p.Phe56Val Benign same condition
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

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-tyr128cys (accessed [today's date]).

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