Is ARMC2 p.Lys428fs (c.1284_1288del) pathogenic?

ARMC2 p.Lys428fs (c.12841288del) is classified Pathogenic in ARMC2 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2019-05-15). Very rare (popmax 0.00017%, nfe); Associated with male infertility with teratozoospermia due to single gene mutation.

How common is ARMC2 p.Lys428fs (c.1284_1288del) in the general population?

ARMC2 p.Lys428fs (c.1284_1288del) is very rare (popmax 0.00017%, nfe) (gnomAD).

ARMC2 p.Lys428fs

Q: What condition is associated with ARMC2 p.Lys428fs (c.1284_1288del)?

ARMC2 p.Lys428fs (c.1284_1288del) is associated with male infertility with teratozoospermia due to single gene mutation, spermatogenic failure 38 (ClinVar).

c.1284_1288del · rs1562381747 · VCV627630

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

male infertility with teratozoospermia due to single gene mutation

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 10 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.2	GERP 2.7, phastCons 1
Overall
CADD	28.8	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 0.00017% European (non-Finnish) · 2/1,179,894 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,870 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: ARMC2
Protein: p.Lys428fs
Coding: c.1284_1288del
MANE Select: NM_032131
dbSNP: rs1562381747
Type: Deletion
Location: chr6:108912489 (GRCh38)
Gene constraint: LOEUF 0.936 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.57
Residue 428: a UniProt-annotated variant site (in spgf38; uncertain significance)

Full ARMC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

male infertility with teratozoospermia due to single gene mutation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: spermatogenic failure 38

For Male infertility with teratozoospermia due to single gene mutation (Orphanet):

Onset: Adolescent, Adult

Similar variants

ARMC2 p.Leu785fs Pathogenic same condition
ARMC2 c.2153-1G>C Likely pathogenic ★ same condition
ARMC2 p.Lys228Arg Uncertain significance ★ ⚠ same condition
ARMC2 c.1023+1G>A Pathogenic same condition
ARMC2 p.Gln141Ter Pathogenic same condition
ARMC2 p.Ile760Asn 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/armc2-p-lys428fs (accessed [today's date]).

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