Is CPT2 p.Pro211Ser (c.631C>T) pathogenic?

CPT2 p.Pro211Ser (c.631C>T) is classified Conflicting classifications of pathogenicity in CPT2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-02-22). AlphaMissense: likely pathogenic (0.9378); Very rare (popmax 0.0011%, sas); Associated with carnitine palmitoyl transferase II deficiency, neonatal form.

How common is CPT2 p.Pro211Ser (c.631C>T) in the general population?

CPT2 p.Pro211Ser (c.631C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

How is Carnitine palmitoyltransferase II deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CPT2 p.Pro211Ser (c.631C>T)?

AlphaMissense predicts likely pathogenic (score 0.9378) — an in-silico prediction, not a clinical call.

CPT2 p.Pro211Ser

Q: What condition is associated with CPT2 p.Pro211Ser (c.631C>T)?

CPT2 p.Pro211Ser (c.631C>T) is associated with carnitine palmitoyl transferase II deficiency, neonatal form, carnitine palmitoyl transferase II deficiency, myopathic form, carnitine palmitoyl transferase II deficiency, severe infantile form (ClinVar).

c.631C>T · rs796051942 · VCV2688862

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9378 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

carnitine palmitoyl transferase II deficiency, neonatal form

Computational evidence

Protein change
AlphaMissense	0.9378	likely pathogenic
REVEL	0.91	moderately pathogenic-leaning
SaProt	LLR -11.63	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 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 17 kb · p 0.062 · regional, not allelic
Overall
CADD	25.5	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 0.0011% South Asian · 1/91,086 alleles

Overall 0.000137% 2/1,461,860 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,508
South Asiangrpmax	0.0011%	91,086

Remaining individuals 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: CPT2
Protein: p.Pro211Ser
Coding: c.631C>T
MANE Select: NM_000098
dbSNP: rs796051942
Type: single nucleotide variant
Location: chr1:53210305 (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

carnitine palmitoyl transferase II deficiency, neonatal form — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: carnitine palmitoyl transferase II deficiency, myopathic form carnitine palmitoyl transferase II deficiency, severe infantile form encephalopathy, acute, infection-induced, susceptibility to, 4

For Carnitine palmitoyltransferase II deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages

Similar variants

CPT2 p.Pro211fs Pathogenic/Likely pathogenic ★★ same residue
CPT2 p.Pro211Leu Uncertain significance ★ same residue
CPT2 p.Pro211= Likely benign ★ same residue
CPT2 c.340+5G>A Likely pathogenic ★★ same condition
CPT2 c.341-2A>G Pathogenic/Likely pathogenic ★★ same condition
CPT2 p.Ala67Gly Likely pathogenic ★★ ⚠ same condition
CPT2 p.Arg124Gln Likely pathogenic ★★ ⚠ same condition
CPT2 p.Arg124Ter 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-pro211ser (accessed [today's date]).

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