Is ARMC5 p.Ser533fs (c.1597del) pathogenic?

ARMC5 p.Ser533fs (c.1597del) is classified Uncertain significance in ARMC5 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2018-09-16). Very rare (popmax 6.93e-05%).

How common is ARMC5 p.Ser533fs (c.1597del) in the general population?

ARMC5 p.Ser533fs (c.1597del) is very rare (popmax 6.93e-05%) (gnomAD).

ARMC5 p.Ser533fs

c.1597del · rs1567377180 · VCV591035

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 6.93e-05%)

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 4 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.29	GERP 1.7, phastCons 0.98

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.93e-05%

Overall 6.93e-05% 1/1,443,398 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: ARMC5
Protein: p.Ser533fs
Coding: c.1597del
MANE Select: NM_001105247
dbSNP: rs1567377180
Type: Deletion
Location: chr16:31464617 (GRCh38)
Gene constraint: LOEUF 0.772 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.27
Residue 533: 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

Similar variants

ARMC5 c.476-374_1370+221del Likely pathogenic ★ same type
ARMC5 p.Gly108fs Likely pathogenic ★ same type
ARMC5 p.Ile515fs Likely pathogenic ★ same type
ARMC5 p.Leu199fs Pathogenic ★ same type
ARMC5 p.Leu373fs Likely pathogenic ★ same type
ARMC5 p.Pro501fs Likely pathogenic ★ same type
ARMC5 p.Pro602fs Likely pathogenic ★ same type
ARMC5 p.Pro731fs 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/armc5-p-ser533fs (accessed [today's date]).

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