Is CPT1C p.Arg338Trp (c.1012C>T) pathogenic?

CPT1C p.Arg338Trp (c.1012C>T) is classified Uncertain significance in CPT1C (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-10). AlphaMissense: likely benign (0.2092); Very rare (popmax 0.00891%, eas).

How common is CPT1C p.Arg338Trp (c.1012C>T) in the general population?

CPT1C p.Arg338Trp (c.1012C>T) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about CPT1C p.Arg338Trp (c.1012C>T)?

AlphaMissense predicts likely benign (score 0.2092) — an in-silico prediction, not a clinical call.

CPT1C p.Arg338Trp

c.1012C>T · VCV3496659

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2092 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2092	likely benign
REVEL	0.523	indeterminate
SaProt	LLR -14.14	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ1.00 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.1	phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 15 kb · p 0.77 · regional, not allelic
Overall
CADD	26.8	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

Grpmax group 0.00891% East Asian · 4/44,880 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00151% 22/1,461,708 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,220
European (non-Finnish)	0.00144%	69,408
South Asian	0.0011%	91,066

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.Arg338Trp
Coding: c.1012C>T
MANE Select: NM_001199753
Type: single nucleotide variant
Location: chr19:49705956 (GRCh38)
Gene constraint: LOEUF 0.778 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.81 · 1 PDB

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

Similar variants

CPT1C p.Arg338= Uncertain significance ★ same residue
CPT1C p.Arg338Gln Uncertain significance ★ ⚠ same residue
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

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-arg338trp (accessed [today's date]).

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