Is APOD p.Phe15Ser (c.44T>C) pathogenic?

APOD p.Phe15Ser (c.44T>C) is classified Benign in APOD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2018-07-29). AlphaMissense: likely benign (0.1034); Rare (popmax 0.726%, mid).

How common is APOD p.Phe15Ser (c.44T>C) in the general population?

APOD p.Phe15Ser (c.44T>C) is rare (popmax 0.726%, mid) (gnomAD).

What do computational predictors say about APOD p.Phe15Ser (c.44T>C)?

AlphaMissense predicts likely benign (score 0.1034) — an in-silico prediction, not a clinical call.

APOD p.Phe15Ser

c.44T>C · rs5952 · VCV769625

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1034 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.726%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1034	likely benign
REVEL	0.191	benign-leaning
SaProt	LLR -5.90	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 5.9	GERP -0.52, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 11 kb · p 0.66 · regional, not allelic
Overall
CADD	15.42	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 0.726% Middle Eastern · 44/6,062 alleles

Filtering AF 0.556% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.51%

Overall 0.461% 7,443/1,614,068 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.726%	138
Finnishnot grpmax-eligible	0.705%	142
European (non-Finnish)	0.526%	190
Admixed American	0.503%	199
Remaining individualsnot grpmax-eligible	0.45%	222
Amishnot grpmax-eligible	0.439%	228
African / African-American	0.0893%	1,120
Ashkenazi Jewishnot grpmax-eligible	0.0844%	1,184
South Asian	0.0692%	1,446

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.Phe15Ser
Coding: c.44T>C
MANE Select: NM_001647
dbSNP: rs5952
Type: single nucleotide variant
Location: chr3:195579418 (GRCh38)
Gene constraint: LOEUF 1.436 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.57 · 2 PDB
Residue 15: a UniProt-annotated variant site (in)

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

Similar variants

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
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-phe15ser (accessed [today's date]).

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