Is ACAD11 p.Trp415Leu (c.1244G>T) pathogenic?

ACAD11 p.Trp415Leu (c.1244G>T) is classified Uncertain significance in ACAD11 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-19). AlphaMissense: ambiguous (0.5449); Very rare (popmax 8.53e-05%, nfe).

How common is ACAD11 p.Trp415Leu (c.1244G>T) in the general population?

ACAD11 p.Trp415Leu (c.1244G>T) is very rare (popmax 8.53e-05%, nfe) (gnomAD).

What do computational predictors say about ACAD11 p.Trp415Leu (c.1244G>T)?

AlphaMissense predicts ambiguous (score 0.5449) — an in-silico prediction, not a clinical call.

ACAD11 p.Trp415Leu

c.1244G>T · rs2530105714 · VCV2336566

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5449 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.53e-05%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5449	ambiguous
REVEL	0.66	pathogenic-leaning
SaProt	LLR -11.61	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.40 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6	GERP 2.7, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 101 kb · p 0.1 · regional, not allelic
Overall
CADD	26.7	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 8.53e-05% European (non-Finnish) · 1/1,171,764 alleles

Overall 6.94e-05% 1/1,440,472 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: ACAD11
Protein: p.Trp415Leu
Coding: c.1244G>T
MANE Select: NM_032169
dbSNP: rs2530105714
Type: single nucleotide variant
Location: chr3:132619499 (GRCh38)
Gene constraint: LOEUF 1.01 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.00 · 1 PDB

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-trp415leu (accessed [today's date]).

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