Is ACAD10 p.Phe464Ile (c.1390T>A) pathogenic?

ACAD10 p.Phe464Ile (c.1390T>A) is classified Uncertain significance in ACAD10 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-25). AlphaMissense: likely pathogenic (0.9035); Very rare (popmax 0.00223%, eas).

How common is ACAD10 p.Phe464Ile (c.1390T>A) in the general population?

ACAD10 p.Phe464Ile (c.1390T>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about ACAD10 p.Phe464Ile (c.1390T>A)?

AlphaMissense predicts likely pathogenic (score 0.9035) — an in-silico prediction, not a clinical call.

ACAD10 p.Phe464Ile

c.1390T>A · rs753056489 · VCV2540225

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9035 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9035	likely pathogenic · top 6% in ACAD10
REVEL	0.51	indeterminate
SaProt	LLR -14.29	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 5.2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 64 kb · p 0.013 · regional, not allelic
Overall
CADD	27.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00223% East Asian · 1/44,840 alleles

Overall 0.000205% 3/1,461,238 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,840
Remaining individualsnot grpmax-eligible	0.0016%	62,484
European (non-Finnish)	8.48e-05%	1,179,626

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.Phe464Ile
Coding: c.1390T>A
MANE Select: NM_025247
dbSNP: rs753056489
Type: single nucleotide variant
Location: chr12:111729952 (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-phe464ile (accessed [today's date]).

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