Is CPT1A p.Ser34Pro (c.100T>C) pathogenic?

CPT1A p.Ser34Pro (c.100T>C) is classified Conflicting classifications of pathogenicity in CPT1A (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-11-03). AlphaMissense: likely pathogenic (0.9028); Absent from gnomAD v4.1; Associated with CPT1A-related disorder.

What condition is associated with CPT1A p.Ser34Pro (c.100T>C)?

CPT1A p.Ser34Pro (c.100T>C) is associated with CPT1A-related disorder, carnitine palmitoyl transferase 1A deficiency (ClinVar).

How common is CPT1A p.Ser34Pro (c.100T>C) in the general population?

CPT1A p.Ser34Pro (c.100T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CPT1A p.Ser34Pro (c.100T>C)?

AlphaMissense predicts likely pathogenic (score 0.9028) — an in-silico prediction, not a clinical call.

CPT1A p.Ser34Pro

c.100T>C · rs398123653 · VCV93971

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.9028 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CPT1A-related disorder

Computational evidence

Protein change
AlphaMissense	0.9028	likely pathogenic
REVEL	0.65	pathogenic-leaning
SaProt	LLR -9.73	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.8	GERP 0.68, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 11 kb · p 0.094 · regional, not allelic
Overall
CADD	22.8	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: CPT1A
Protein: p.Ser34Pro
Coding: c.100T>C
MANE Select: NM_001876
dbSNP: rs398123653
Type: single nucleotide variant
Location: chr11:68815375 (GRCh38)
Gene constraint: LOEUF 0.709 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 92.55 · 1 PDB
Residue 34: an α-helix

Full CPT1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CPT1A-related disorder

Also linked: carnitine palmitoyl transferase 1A deficiency

Similar variants

CPT1A p.Ser34Phe Likely pathogenic ★ ⚠ same residue
CPT1A p.Ser34fs Pathogenic ★ same residue
CPT1A c.1163+1G>A Pathogenic/Likely pathogenic ★★ same condition
CPT1A c.1163+2T>C Pathogenic/Likely pathogenic ★★ same condition
CPT1A c.1352+1G>C Likely pathogenic ★★ same condition
CPT1A c.1459-1G>A Likely pathogenic ★★ same condition
CPT1A c.1575+1G>T Likely pathogenic ★★ same condition
CPT1A c.2028+2T>G 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/cpt1a-p-ser34pro (accessed [today's date]).

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