Is CPT1B p.Ala577Gly (c.1730C>G) pathogenic?

CPT1B p.Ala577Gly (c.1730C>G) is classified Uncertain significance in CPT1B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-25). AlphaMissense: likely benign (0.2241); Very rare (popmax 0.005%, amr).

How common is CPT1B p.Ala577Gly (c.1730C>G) in the general population?

CPT1B p.Ala577Gly (c.1730C>G) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about CPT1B p.Ala577Gly (c.1730C>G)?

AlphaMissense predicts likely benign (score 0.2241) — an in-silico prediction, not a clinical call.

CPT1B p.Ala577Gly

c.1730C>G · VCV4233608

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2241 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2241	likely benign
REVEL	0.953	strongly pathogenic-leaning
SaProt	LLR -7.70	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.5, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 8,574 bp · p 0.28 · regional, not allelic
Overall
CADD	29.4	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 0.005% Admixed American · 3/60,034 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000205% 3/1,461,488 alleles · very rare

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.Ala577Gly
Coding: c.1730C>G
MANE Select: NM_152246
Type: single nucleotide variant
Location: chr22:50571385 (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.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.Ile412Val 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-ala577gly (accessed [today's date]).

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