Is ACAD10 p.Pro452Ala (c.1354C>G) pathogenic?

ACAD10 p.Pro452Ala (c.1354C>G) is classified Uncertain significance in ACAD10 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-06). AlphaMissense: ambiguous (0.5199); Very rare (popmax 0.00223%, eas).

How common is ACAD10 p.Pro452Ala (c.1354C>G) in the general population?

ACAD10 p.Pro452Ala (c.1354C>G) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about ACAD10 p.Pro452Ala (c.1354C>G)?

AlphaMissense predicts ambiguous (score 0.5199) — an in-silico prediction, not a clinical call.

ACAD10 p.Pro452Ala

c.1354C>G · rs771935027 · VCV2295464

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5199 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Computational evidence

Protein change
AlphaMissense	0.5199	ambiguous
REVEL	0.37	indeterminate
SaProt	LLR -14.24	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 4.3, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 64 kb · p 0.013 · regional, not allelic
Overall
CADD	23.4	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 0.00223% East Asian · 1/44,882 alleles

Overall 0.000137% 2/1,461,846 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,882
Admixed American	0.00167%	60,014

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: ACAD10
Protein: p.Pro452Ala
Coding: c.1354C>G
MANE Select: NM_025247
dbSNP: rs771935027
Type: single nucleotide variant
Location: chr12:111729916 (GRCh38)
Gene constraint: LOEUF 1.05 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.83

Full ACAD10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACAD10 p.Ala1000Ser Uncertain significance ★ ⚠ same type
ACAD10 p.Ala1014Val Uncertain significance ★ ⚠ same type
ACAD10 p.Ala1048Val Uncertain significance ★ ⚠ same type
ACAD10 p.Ala222Ser Uncertain significance ★ ⚠ same type
ACAD10 p.Ala44Val Uncertain significance ★ ⚠ same type
ACAD10 p.Ala593Thr Uncertain significance ★ ⚠ same type
ACAD10 p.Ala597Thr Uncertain significance ★ ⚠ same type
ACAD10 p.Ala910Val 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/acad10-p-pro452ala (accessed [today's date]).

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