Is ARMC5 p.Ile58fs (c.170dup) pathogenic?

ARMC5 p.Ile58fs (c.170dup) is classified Likely pathogenic in ARMC5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-26). Very rare (popmax 0.00277%, afr).

How common is ARMC5 p.Ile58fs (c.170dup) in the general population?

ARMC5 p.Ile58fs (c.170dup) is very rare (popmax 0.00277%, afr) (gnomAD).

ARMC5 p.Ile58fs

c.170dup · VCV4532321

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00277%, afr)

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 3.9	GERP 0.92, phastCons 1
Overall
CADD	32.0	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 0.00277% African / African-American · 2/72,188 alleles

Filtering AF 0.00046% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000172%

Overall 0.000509% 8/1,570,748 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00358%	27,902
African / African-Americangrpmax	0.00277%	36,094
European (non-Finnish)	0.000428%	233,745

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ile58fs
Coding: c.170dup
MANE Select: NM_001105247
Type: Duplication
Location: chr16:31459688 (GRCh38)
Gene constraint: LOEUF 0.772 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.27
Residue 58: 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 p.Ile58= Benign ★★ same residue
ARMC5 p.Ala409fs Pathogenic ★ same type
ARMC5 p.Val114fs Pathogenic ★ same type
ARMC5 p.Ala110fs Pathogenic same type
ARMC5 p.Glu59fs 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-ile58fs (accessed [today's date]).

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