Is ARMC5 p.Arg267Ter (c.799C>T) pathogenic?

ARMC5 p.Arg267Ter (c.799C>T) is classified Pathogenic in ARMC5 (ClinVar, Single submitter, 2 submitters; last evaluated 2019-08-26). Very rare (popmax 0.00401%, afr); Associated with ARMC5-related disorder.

What condition is associated with ARMC5 p.Arg267Ter (c.799C>T)?

ARMC5 p.Arg267Ter (c.799C>T) is associated with ARMC5-related disorder, ACTH-independent macronodular adrenal hyperplasia 2 (ClinVar).

How common is ARMC5 p.Arg267Ter (c.799C>T) in the general population?

ARMC5 p.Arg267Ter (c.799C>T) is very rare (popmax 0.00401%, afr) (gnomAD).

ARMC5 p.Arg267Ter

c.799C>T · rs369721476 · VCV144052

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Conditions

ARMC5-related disorder

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 3 of 6
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 1, phastCons 1
Overall
CADD	36.0	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 0.00401% African / African-American · 3/74,900 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000931% 15/1,610,430 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,967
South Asian	0.0011%	90,998
European (non-Finnish)	0.000933%	107,167

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: ARMC5
Protein: p.Arg267Ter
Coding: c.799C>T
MANE Select: NM_001105247
dbSNP: rs369721476
Type: single nucleotide variant
Location: chr16:31462346 (GRCh38)
Gene constraint: LOEUF 0.772 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.27
Residue 267: a UniProt-annotated variant site (in aimah2; uncertain significance); a UniProt-annotated variant site (in aimah2)

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

Disease context

ARMC5-related disorder

Also linked: ACTH-independent macronodular adrenal hyperplasia 2

Similar variants

ARMC5 p.Arg267Gln Likely benign ★ same residue
ARMC5 p.Arg173Ter Pathogenic ★★ same condition
ARMC5 p.Arg690Gln Uncertain significance ★★ ⚠ same condition
ARMC5 p.Pro606Leu Uncertain significance ★★ ⚠ same condition
ARMC5 p.Trp801Cys Uncertain significance ★★ ⚠ same condition
ARMC5 p.Ala243= Benign/Likely benign ★★ same condition
ARMC5 p.Leu156Phe Benign/Likely benign ★★ same condition
ARMC5 p.Arg315Pro Likely 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-arg267ter (accessed [today's date]).

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