Is CPT1C p.Ser44Pro (c.130T>C) pathogenic?

CPT1C p.Ser44Pro (c.130T>C) is classified Uncertain significance in CPT1C (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-08). AlphaMissense: likely benign (0.1636); Very rare (popmax 0.00223%, eas).

How common is CPT1C p.Ser44Pro (c.130T>C) in the general population?

CPT1C p.Ser44Pro (c.130T>C) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CPT1C p.Ser44Pro (c.130T>C)?

AlphaMissense predicts likely benign (score 0.1636) — an in-silico prediction, not a clinical call.

CPT1C p.Ser44Pro

c.130T>C · VCV4656294

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1636 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1636	likely benign
REVEL	0.39	indeterminate
SaProt	LLR -10.76	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.18
Regional constraint	o/e 0.99	unconstrained · MANE · 15 kb · p 0.77 · regional, not allelic
Overall
CADD	19.84	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 0.00223% East Asian · 1/44,868 alleles

Overall 0.000137% 2/1,461,808 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,868
European (non-Finnish)	8.47e-05%	1,179,979

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: CPT1C
Protein: p.Ser44Pro
Coding: c.130T>C
MANE Select: NM_001199753
Type: single nucleotide variant
Location: chr19:49692382 (GRCh38)
Gene constraint: LOEUF 0.778 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.81 · 1 PDB
Residue 44: an α-helix

Full CPT1C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CPT1C c.1160+3A>G Uncertain significance ★★ same type
CPT1C p.Ala117Val Uncertain significance ★★ ⚠ same type
CPT1C p.Ala19Thr Uncertain significance ★★ ⚠ same type
CPT1C p.Ala203Thr Uncertain significance ★★ ⚠ same type
CPT1C p.Ala401Val Uncertain significance ★★ ⚠ same type
CPT1C p.Ala422Thr Uncertain significance ★★ ⚠ same type
CPT1C p.Ala431Val Uncertain significance ★★ ⚠ same type
CPT1C p.Ala4Glu 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/cpt1c-p-ser44pro (accessed [today's date]).

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