Is ARMC2 p.Pro622= (c.1866G>A) pathogenic?

ARMC2 p.Pro622= (c.1866G>A) is classified Likely benign in ARMC2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-12-09). Ultra-rare (popmax 0.0678%, nfe); Associated with ARMC2-related disorder.

What condition is associated with ARMC2 p.Pro622= (c.1866G>A)?

ARMC2 p.Pro622= (c.1866G>A) is associated with ARMC2-related disorder (ClinVar).

How common is ARMC2 p.Pro622= (c.1866G>A) in the general population?

ARMC2 p.Pro622= (c.1866G>A) is ultra-rare (popmax 0.0678%, nfe) (gnomAD).

ARMC2 p.Pro622=

c.1866G>A · rs199732181 · VCV3048714

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0678%, nfe)

Conditions

ARMC2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -14	GERP -3.9
Overall
CADD	0.072	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0678% European (non-Finnish) · 800/1,179,518 alleles

Filtering AF 0.0639% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0623%

Overall 0.0533% 859/1,610,424 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0678%	1,474
Remaining individualsnot grpmax-eligible	0.0544%	1,837
Admixed American	0.0217%	4,615
African / African-American	0.0147%	6,824
South Asian	0.0011%	91,038

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.Pro622=
Coding: c.1866G>A
MANE Select: NM_032131
dbSNP: rs199732181
Type: single nucleotide variant
Location: chr6:108953302 (GRCh38)
Gene constraint: LOEUF 0.936 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.57
Residue 622: 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

ARMC2-related disorder

Similar variants

ARMC2 p.Ile185Val Conflicting classifications of pathogenicity ⚠ same condition
ARMC2 c.219-4C>T Benign same condition
ARMC2 p.Ala184Val Benign same condition
ARMC2 p.Ala593= Benign same condition
ARMC2 p.Gly438= Benign same condition
ARMC2 p.Ile630Val Benign same condition
ARMC2 p.Met166Thr Benign same condition
ARMC2 p.Pro99= Benign 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-pro622 (accessed [today's date]).

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