Is APOD p.Arg60Cys (c.178C>T) pathogenic?

APOD p.Arg60Cys (c.178C>T) is classified Uncertain significance in APOD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-18). AlphaMissense: ambiguous (0.4044); Ultra-rare (popmax 0.0593%, sas).

How common is APOD p.Arg60Cys (c.178C>T) in the general population?

APOD p.Arg60Cys (c.178C>T) is ultra-rare (popmax 0.0593%, sas) (gnomAD).

What do computational predictors say about APOD p.Arg60Cys (c.178C>T)?

AlphaMissense predicts ambiguous (score 0.4044) — an in-silico prediction, not a clinical call.

APOD p.Arg60Cys

c.178C>T · rs141030350 · VCV2518975

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4044 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0593%, sas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4044	ambiguous
REVEL	0.2	benign-leaning
SaProt	LLR -13.17	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP 0.6, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 11 kb · p 0.66 · regional, not allelic
Overall
CADD	23.6	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 0.0593% South Asian · 54/91,080 alleles

Filtering AF 0.0466% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0421%

Overall 0.00805% 130/1,614,040 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0593%	1,687
East Asian	0.00668%	14,963
European (non-Finnish)	0.00593%	16,858
Remaining individualsnot grpmax-eligible	0.0032%	31,240
Admixed American	0.00167%	60,002

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.Arg60Cys
Coding: c.178C>T
MANE Select: NM_001647
dbSNP: rs141030350
Type: single nucleotide variant
Location: chr3:195573917 (GRCh38)
Gene constraint: LOEUF 1.436 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.57 · 2 PDB
Residue 60: a β-strand; 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.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-arg60cys (accessed [today's date]).

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