Is ACAD11 p.Ser163Pro (c.487T>C) pathogenic?

ACAD11 p.Ser163Pro (c.487T>C) is classified Uncertain significance in ACAD11 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-04). AlphaMissense: likely benign (0.159); Ultra-rare (popmax 0.0284%, nfe).

How common is ACAD11 p.Ser163Pro (c.487T>C) in the general population?

ACAD11 p.Ser163Pro (c.487T>C) is ultra-rare (popmax 0.0284%, nfe) (gnomAD).

What do computational predictors say about ACAD11 p.Ser163Pro (c.487T>C)?

AlphaMissense predicts likely benign (score 0.159) — an in-silico prediction, not a clinical call.

ACAD11 p.Ser163Pro

c.487T>C · rs140456617 · VCV3134593

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.159 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0284%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.159	likely benign
REVEL	0.216	benign-leaning
SaProt	LLR -11.76	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	GERP -0.56, phastCons 0.99
Regional constraint	o/e 0.95	unconstrained · MANE · 101 kb · p 0.1 · regional, not allelic
Overall
CADD	22.0	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 0.0284% European (non-Finnish) · 335/1,179,916 alleles

Filtering AF 0.0259% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0249%

Overall 0.0218% 352/1,614,028 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0284%	3,522
Remaining individualsnot grpmax-eligible	0.0208%	4,808
African / African-American	0.00533%	18,760

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.Ser163Pro
Coding: c.487T>C
MANE Select: NM_032169
dbSNP: rs140456617
Type: single nucleotide variant
Location: chr3:132642022 (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-ser163pro (accessed [today's date]).

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