Is ACAD11 p.Pro16Ser (c.46C>T) pathogenic?

ACAD11 p.Pro16Ser (c.46C>T) is classified Uncertain significance in ACAD11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-17). AlphaMissense: likely benign (0.0958); Ultra-rare (popmax 0.0441%, afr).

How common is ACAD11 p.Pro16Ser (c.46C>T) in the general population?

ACAD11 p.Pro16Ser (c.46C>T) is ultra-rare (popmax 0.0441%, afr) (gnomAD).

What do computational predictors say about ACAD11 p.Pro16Ser (c.46C>T)?

AlphaMissense predicts likely benign (score 0.0958) — an in-silico prediction, not a clinical call.

ACAD11 p.Pro16Ser

c.46C>T · rs142799108 · VCV2373169

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0958 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0441%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0958	likely benign
REVEL	0.298	indeterminate
SaProt	LLR -9.06	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 5.5	GERP 0.28, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 101 kb · p 0.1 · regional, not allelic
Overall
CADD	19.35	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 0.0441% African / African-American · 33/74,826 alleles

Filtering AF 0.0322% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0281%

Overall 0.00255% 41/1,610,426 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0441%	2,267
Admixed American	0.00671%	14,913
Remaining individualsnot grpmax-eligible	0.00481%	20,785
European (non-Finnish)	8.49e-05%	1,177,922

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.Pro16Ser
Coding: c.46C>T
MANE Select: NM_032169
dbSNP: rs142799108
Type: single nucleotide variant
Location: chr3:132659706 (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-pro16ser (accessed [today's date]).

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