Is CPT1B p.Ile412Val (c.1234A>G) pathogenic?

CPT1B p.Ile412Val (c.1234A>G) is classified Uncertain significance in CPT1B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-05). AlphaMissense: likely benign (0.0615); Very rare (popmax 0.00666%, amr).

How common is CPT1B p.Ile412Val (c.1234A>G) in the general population?

CPT1B p.Ile412Val (c.1234A>G) is very rare (popmax 0.00666%, amr) (gnomAD).

What do computational predictors say about CPT1B p.Ile412Val (c.1234A>G)?

AlphaMissense predicts likely benign (score 0.0615) — an in-silico prediction, not a clinical call.

CPT1B p.Ile412Val

c.1234A>G · VCV4233599

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0615 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00666%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0615	likely benign
REVEL	0.2	benign-leaning
SaProt	LLR -6.60	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -2.4, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 8,574 bp · p 0.28 · regional, not allelic
Overall
CADD	15.63	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00666% Admixed American · 4/60,022 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000342% 5/1,461,348 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00666%	15,006
South Asian	0.0011%	91,086

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: CPT1B
Protein: p.Ile412Val
Coding: c.1234A>G
MANE Select: NM_152246
Type: single nucleotide variant
Location: chr22:50572993 (GRCh38)
Gene constraint: LOEUF 0.742 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.31

Full CPT1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CPT1B p.Ala511Val Uncertain significance ★ ⚠ same type
CPT1B p.Ala577Gly Uncertain significance ★ ⚠ same type
CPT1B p.Arg285His Uncertain significance ★ ⚠ same type
CPT1B p.Arg563Gln Uncertain significance ★ ⚠ same type
CPT1B p.Asn405His Uncertain significance ★ ⚠ same type
CPT1B p.Gln6Arg Uncertain significance ★ ⚠ same type
CPT1B p.Ile242Leu Uncertain significance ★ ⚠ same type
CPT1B p.Leu158Arg 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/cpt1b-p-ile412val (accessed [today's date]).

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