Is ARMC5 p.Ser95fs (c.283_286del) pathogenic?

ARMC5 p.Ser95fs (c.283286del) is classified Pathogenic in ARMC5 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-09-01). Absent from gnomAD; Associated with ACTH-independent macronodular adrenal hyperplasia 2.

What condition is associated with ARMC5 p.Ser95fs (c.283_286del)?

ARMC5 p.Ser95fs (c.283_286del) is associated with ACTH-independent macronodular adrenal hyperplasia 2 (ClinVar).

How common is ARMC5 p.Ser95fs (c.283_286del) in the general population?

ARMC5 p.Ser95fs (c.283_286del) is absent from gnomAD (gnomAD).

ARMC5 p.Ser95fs

Q: How is Cushing syndrome due to bilateral macronodular adrenocortical disease inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

c.283_286del · rs2142562239 · VCV1341364

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

ACTH-independent macronodular adrenal hyperplasia 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.81	GERP -2.1, phastCons 0.001

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ARMC5
Protein: p.Ser95fs
Coding: c.283_286del
MANE Select: NM_001105247
dbSNP: rs2142562239
Type: Deletion
Location: chr16:31459806 (GRCh38)
Gene constraint: LOEUF 0.772 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.27
Residue 95: a UniProt-annotated variant site (in aimah2; uncertain significance); a UniProt-annotated variant site (in aimah2); the 'disordered' region

Full ARMC5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ACTH-independent macronodular adrenal hyperplasia 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Cushing syndrome due to bilateral macronodular adrenocortical disease (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: All ages
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

ARMC5 p.Ile515fs Likely pathogenic ★ same condition
ARMC5 p.Leu373fs Likely pathogenic ★ same condition
ARMC5 c.1864+200del Uncertain significance ★ same condition
ARMC5 p.Ser95Leu Uncertain significance ★ ⚠ same residue
ARMC5 p.Ser95Pro Uncertain significance ★ ⚠ same residue
ARMC5 p.Cys813fs Pathogenic same condition
ARMC5 p.Gly57fs Pathogenic same condition
ARMC5 p.Leu676fs Pathogenic same condition

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/armc5-p-ser95fs (accessed [today's date]).

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