Is APOD p.Pro102Ala (c.304C>G) pathogenic?

APOD p.Pro102Ala (c.304C>G) is classified Uncertain significance in APOD (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-13). AlphaMissense: likely benign (0.1808); Rare (popmax 0.248%, mid).

How common is APOD p.Pro102Ala (c.304C>G) in the general population?

APOD p.Pro102Ala (c.304C>G) is rare (popmax 0.248%, mid) (gnomAD).

What do computational predictors say about APOD p.Pro102Ala (c.304C>G)?

AlphaMissense predicts likely benign (score 0.1808) — an in-silico prediction, not a clinical call.

APOD p.Pro102Ala

c.304C>G · rs146246326 · VCV2355698

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1808 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.248%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1808	likely benign
REVEL	0.12	moderately benign-leaning
SaProt	LLR -11.64	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP -0.3, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 11 kb · p 0.66 · regional, not allelic
Overall
CADD	22.6	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 0.248% Middle Eastern · 15/6,058 alleles

Filtering AF 0.153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.123%

Overall 0.028% 452/1,614,100 alleles · rare exomes 412/1,461,868 · genomes 40/152,232 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.331%	302
Middle Easterngrpmax	0.248%	404
South Asian	0.133%	753
Remaining individualsnot grpmax-eligible	0.0576%	1,736
Admixed American	0.0183%	5,456
European (non-Finnish)	0.0142%	7,066
African / African-American	0.00533%	18,755

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro102Ala
Coding: c.304C>G
MANE Select: NM_001647
dbSNP: rs146246326
Type: single nucleotide variant
Location: chr3:195571307 (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.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-pro102ala (accessed [today's date]).

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