Is ACAD11 p.Pro463Ala (c.1387C>G) pathogenic?

ACAD11 p.Pro463Ala (c.1387C>G) is classified Uncertain significance in ACAD11 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-03). AlphaMissense: likely benign (0.0744); Ultra-rare (popmax 0.0242%, afr).

How common is ACAD11 p.Pro463Ala (c.1387C>G) in the general population?

ACAD11 p.Pro463Ala (c.1387C>G) is ultra-rare (popmax 0.0242%, afr) (gnomAD).

What do computational predictors say about ACAD11 p.Pro463Ala (c.1387C>G)?

AlphaMissense predicts likely benign (score 0.0744) — an in-silico prediction, not a clinical call.

ACAD11 p.Pro463Ala

c.1387C>G · VCV3463083

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0744 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0242%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0744	likely benign
REVEL	0.483	indeterminate
SaProt	LLR -8.73	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.1, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 101 kb · p 0.1 · regional, not allelic
Overall
CADD	21.2	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 0.0242% African / African-American · 18/74,314 alleles

Filtering AF 0.0156% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0129%

Overall 0.00112% 18/1,605,132 alleles · ultra-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: ACAD11
Protein: p.Pro463Ala
Coding: c.1387C>G
MANE Select: NM_032169
Type: single nucleotide variant
Location: chr3:132618661 (GRCh38)
Gene constraint: LOEUF 1.01 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.00 · 1 PDB
Residue 463: an α-helix

Full ACAD11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACAD11 p.Ala191Thr Uncertain significance ★ ⚠ same type
ACAD11 p.Ala516Val Uncertain significance ★ ⚠ same type
ACAD11 p.Ala550Pro Uncertain significance ★ ⚠ same type
ACAD11 p.Ala646Thr Uncertain significance ★ ⚠ same type
ACAD11 p.Ala680Gly Uncertain significance ★ ⚠ same type
ACAD11 p.Ala725Pro Uncertain significance ★ ⚠ same type
ACAD11 p.Ala741Val Uncertain significance ★ ⚠ same type
ACAD11 p.Ala765Thr 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/acad11-p-pro463ala (accessed [today's date]).

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