Is CPT1A p.Cys562Ser (c.1685G>C) pathogenic?

CPT1A p.Cys562Ser (c.1685G>C) is classified Uncertain significance in CPT1A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-17). AlphaMissense: ambiguous (0.3498); Ultra-rare (popmax 0.03%, amr); Associated with carnitine palmitoyl transferase 1A deficiency.

What condition is associated with CPT1A p.Cys562Ser (c.1685G>C)?

CPT1A p.Cys562Ser (c.1685G>C) is associated with carnitine palmitoyl transferase 1A deficiency (ClinVar).

How common is CPT1A p.Cys562Ser (c.1685G>C) in the general population?

CPT1A p.Cys562Ser (c.1685G>C) is ultra-rare (popmax 0.03%, amr) (gnomAD).

How is Carnitine palmitoyl transferase 1A deficiency inherited?

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

What do computational predictors say about CPT1A p.Cys562Ser (c.1685G>C)?

AlphaMissense predicts ambiguous (score 0.3498) — an in-silico prediction, not a clinical call.

CPT1A p.Cys562Ser

c.1685G>C · rs777226313 · VCV2049330

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3498 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.03%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

carnitine palmitoyl transferase 1A deficiency

Computational evidence

Protein change
AlphaMissense	0.3498	ambiguous
REVEL	0.279	benign-leaning
SaProt	LLR -6.95	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP 1, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 46 kb · p 1.1e-09 · regional, not allelic
Overall
CADD	19.43	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 0.03% Admixed American · 18/59,994 alleles

Filtering AF 0.0194% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.016%

Overall 0.0018% 29/1,614,080 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.03%	3,333
Remaining individualsnot grpmax-eligible	0.0032%	31,245
European (non-Finnish)	0.000763%	131,117

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: CPT1A
Protein: p.Cys562Ser
Coding: c.1685G>C
MANE Select: NM_001876
dbSNP: rs777226313
Type: single nucleotide variant
Location: chr11:68773320 (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 562: a binding site

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

Disease context

carnitine palmitoyl transferase 1A deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Carnitine palmitoyl transferase 1A deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

CPT1A p.Cys562= Likely benign ★ 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
CPT1A c.281+1G>A 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-cys562ser (accessed [today's date]).

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