Is ARMC9 p.Ser55fs (c.162dup) pathogenic?

ARMC9 p.Ser55fs (c.162dup) is classified Pathogenic/Likely pathogenic in ARMC9 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-12). Very rare (popmax 0.00402%, afr); Associated with ARMC9-related disorder.

What condition is associated with ARMC9 p.Ser55fs (c.162dup)?

ARMC9 p.Ser55fs (c.162dup) is associated with ARMC9-related disorder (ClinVar).

How common is ARMC9 p.Ser55fs (c.162dup) in the general population?

ARMC9 p.Ser55fs (c.162dup) is very rare (popmax 0.00402%, afr) (gnomAD).

ARMC9 p.Ser55fs

c.162dup · rs763539113 · VCV1431518

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00402%, afr)

Conditions

ARMC9-related disorder

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 3 of 25
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.55	GERP -2.9
Overall
CADD	24.8	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 0.00402% African / African-American · 3/74,612 alleles

Filtering AF 0.00107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000496%

Overall 0.000249% 4/1,607,954 alleles · very rare exomes 2/1,455,864 · genomes 2/152,090 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00402%	24,871
European (non-Finnish)	8.49e-05%	1,177,382

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: ARMC9
Protein: p.Ser55fs
Coding: c.162dup
MANE Select: NM_001352754
dbSNP: rs763539113
Type: Duplication
Location: chr2:231208234 (GRCh38)
Gene constraint: LOEUF 0.975 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.71

Full ARMC9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ARMC9-related disorder

Similar variants

ARMC9 p.Gln519fs Pathogenic/Likely pathogenic ★★ same condition
ARMC9 c.1773+1G>A Likely pathogenic ★★ same condition
ARMC9 c.178-1G>A Likely pathogenic ★★ same condition
ARMC9 p.Arg299Ter Pathogenic/Likely pathogenic ★★ same condition
ARMC9 p.Arg343Cys Pathogenic/Likely pathogenic ★★ same condition
ARMC9 p.Arg87Ter Pathogenic/Likely pathogenic ★★ same condition
ARMC9 p.Val506fs Pathogenic/Likely pathogenic ★★ same condition
ARMC9 p.Asp590del Uncertain significance ★★ 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/armc9-p-ser55fs (accessed [today's date]).

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