Is CPT2 p.Ser506Phe (c.1517C>T) pathogenic?

CPT2 p.Ser506Phe (c.1517C>T) is classified Likely pathogenic in CPT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-04). AlphaMissense: likely pathogenic (0.9591); Absent from gnomAD v4.1; Associated with CPT2-related disorder.

What condition is associated with CPT2 p.Ser506Phe (c.1517C>T)?

CPT2 p.Ser506Phe (c.1517C>T) is associated with CPT2-related disorder (ClinVar).

How common is CPT2 p.Ser506Phe (c.1517C>T) in the general population?

CPT2 p.Ser506Phe (c.1517C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CPT2 p.Ser506Phe (c.1517C>T)?

AlphaMissense predicts likely pathogenic (score 0.9591) — an in-silico prediction, not a clinical call.

CPT2 p.Ser506Phe

c.1517C>T · VCV4974126

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9591 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CPT2-related disorder

Computational evidence

Protein change
AlphaMissense	0.9591	likely pathogenic ✓ concordant with ClinVar · top 8% in CPT2
REVEL	0.91	moderately pathogenic-leaning
SaProt	LLR -13.31	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 17 kb · p 0.062 · regional, not allelic
Overall
CADD	26.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CPT2
Protein: p.Ser506Phe
Coding: c.1517C>T
MANE Select: NM_000098
Type: single nucleotide variant
Location: chr1:53211191 (GRCh38)
Gene constraint: LOEUF 1.038 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.52

Full CPT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CPT2-related disorder

Similar variants

CPT2 p.Ser506= Likely benign ★★ same residue
CPT2 c.340+1G>C Pathogenic/Likely pathogenic ★★ same condition
CPT2 p.Arg124Gln Likely pathogenic ★★ same condition
CPT2 p.Arg124Ter Pathogenic/Likely pathogenic ★★ same condition
CPT2 p.Arg151Trp Pathogenic ★★ same condition
CPT2 p.Arg503Cys Pathogenic/Likely pathogenic ★★ same condition
CPT2 p.Arg631Cys Pathogenic ★★ ⚠ same condition
CPT2 p.His555Gln Pathogenic/Likely pathogenic ★★ same condition

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/cpt2-p-ser506phe (accessed [today's date]).

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