Is APOD p.Phe56Val (c.166T>G) pathogenic?

APOD p.Phe56Val (c.166T>G) is classified Benign in APOD (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-24). AlphaMissense: likely pathogenic (0.8603); Low-frequency (popmax 1.02%, afr); Associated with APOD-related disorder.

What condition is associated with APOD p.Phe56Val (c.166T>G)?

APOD p.Phe56Val (c.166T>G) is associated with APOD-related disorder (ClinVar).

How common is APOD p.Phe56Val (c.166T>G) in the general population?

APOD p.Phe56Val (c.166T>G) is low-frequency (popmax 1.02%, afr) (gnomAD).

What do computational predictors say about APOD p.Phe56Val (c.166T>G)?

AlphaMissense predicts likely pathogenic (score 0.8603) — an in-silico prediction, not a clinical call.

APOD p.Phe56Val

c.166T>G · rs144811342 · VCV3044850

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8603 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.02%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

APOD-related disorder

Computational evidence

Protein change
AlphaMissense	0.8603	likely pathogenic
REVEL	0.494	indeterminate
SaProt	LLR -10.83	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 9.2	GERP 1.7, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 11 kb · p 0.66 · regional, not allelic
Overall
CADD	24.5	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 1.02% African / African-American · 762/75,018 alleles

Filtering AF 0.956% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.932%

Overall 0.0527% 850/1,614,094 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.02%	98
Admixed American	0.0666%	1,500
Remaining individualsnot grpmax-eligible	0.064%	1,563
South Asian	0.0011%	91,074
European (non-Finnish)	0.000593%	168,573

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.Phe56Val
Coding: c.166T>G
MANE Select: NM_001647
dbSNP: rs144811342
Type: single nucleotide variant
Location: chr3:195573929 (GRCh38)
Gene constraint: LOEUF 1.436 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.57 · 2 PDB
Residue 56: 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.Tyr128Cys Likely 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-phe56val (accessed [today's date]).

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