Is ARMC2 p.Gln141Ter (c.421C>T) pathogenic?

ARMC2 p.Gln141Ter (c.421C>T) is classified Pathogenic in ARMC2 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2019-05-15). Absent from gnomAD v4.1; Associated with male infertility with teratozoospermia due to single gene mutation.

How common is ARMC2 p.Gln141Ter (c.421C>T) in the general population?

ARMC2 p.Gln141Ter (c.421C>T) is absent from gnomAD v4.1 (gnomAD).

ARMC2 p.Gln141Ter

Q: What condition is associated with ARMC2 p.Gln141Ter (c.421C>T)?

ARMC2 p.Gln141Ter (c.421C>T) is associated with male infertility with teratozoospermia due to single gene mutation, spermatogenic failure 38 (ClinVar).

c.421C>T · rs1562332833 · VCV627631

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

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	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 18
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.4, phastCons 1
Overall
CADD	38.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ARMC2
Protein: p.Gln141Ter
Coding: c.421C>T
MANE Select: NM_032131
dbSNP: rs1562332833
Type: single nucleotide variant
Location: chr6:108868953 (GRCh38)
Gene constraint: LOEUF 0.936 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.57
Residue 141: 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 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.Ile760Asn Pathogenic ⚠ same condition
ARMC2 p.Leu785fs Pathogenic same condition
ARMC2 p.Lys428fs Pathogenic same condition
ARMC2 p.Asn743Asp Likely pathogenic ★ same type
ARMC2 p.Ala123Val Uncertain significance ★ ⚠ 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/armc2-p-gln141ter (accessed [today's date]).

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