Is ACAD9 p.Arg37Ter (c.109C>T) pathogenic?

ACAD9 p.Arg37Ter (c.109C>T) is classified Pathogenic in ACAD9 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-24). Very rare (popmax 0.00133%, afr).

How common is ACAD9 p.Arg37Ter (c.109C>T) in the general population?

ACAD9 p.Arg37Ter (c.109C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

ACAD9 p.Arg37Ter

c.109C>T · rs936842682 · VCV1393379

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 18
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.3	GERP -3.4
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,914 alleles

Overall 0.000657% 1/152,198 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: ACAD9
Protein: p.Arg37Ter
Coding: c.109C>T
MANE Select: NM_014049
dbSNP: rs936842682
Type: single nucleotide variant
Location: chr3:128879800 (GRCh38)
Gene constraint: LOEUF 0.884 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.09 · 2 PDB

Full ACAD9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACAD9 c.1030-1G>A Pathogenic/Likely pathogenic ★★ same type
ACAD9 c.1150-2A>G Likely pathogenic ★★ same type
ACAD9 c.1278+1G>T Likely pathogenic ★★ same type
ACAD9 c.1279-2A>C Likely pathogenic ★★ same type
ACAD9 c.1358+2T>G Likely pathogenic ★★ same type
ACAD9 c.1359-1G>A Pathogenic/Likely pathogenic ★★ same type
ACAD9 c.1563+1G>A Pathogenic/Likely pathogenic ★★ same type
ACAD9 c.1A>G Pathogenic/Likely pathogenic ★★ 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/acad9-p-arg37ter (accessed [today's date]).

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