Is ARMC2 p.Ala593= (c.1779G>A) pathogenic?

ARMC2 p.Ala593= (c.1779G>A) is classified Benign in ARMC2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-11-08). Low-frequency (popmax 4.16%, mid); Associated with ARMC2-related disorder.

What condition is associated with ARMC2 p.Ala593= (c.1779G>A)?

ARMC2 p.Ala593= (c.1779G>A) is associated with ARMC2-related disorder (ClinVar).

How common is ARMC2 p.Ala593= (c.1779G>A) in the general population?

ARMC2 p.Ala593= (c.1779G>A) is low-frequency (popmax 4.16%, mid) (gnomAD).

ARMC2 p.Ala593=

c.1779G>A · rs41287540 · VCV3060107

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 4.16%, mid)

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 -4.4	GERP -3.5
Overall
CADD	0.538	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.16% Middle Eastern · 252/6,062 alleles

Filtering AF 3.74% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.57%

Overall 1.52% 24,608/1,613,948 alleles · low-frequency

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	6.25%	16
Middle Easterngrpmax	4.16%	24
South Asian	3.14%	32
Ashkenazi Jewishnot grpmax-eligible	3.09%	32
Remaining individualsnot grpmax-eligible	1.76%	57
European (non-Finnish)	1.54%	65
Admixed American	1.5%	67
African / African-American	0.316%	317
Finnishnot grpmax-eligible	0.224%	447
East Asian	0.00446%	22,443

Amish 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: ARMC2
Protein: p.Ala593=
Coding: c.1779G>A
MANE Select: NM_032131
dbSNP: rs41287540
Type: single nucleotide variant
Location: chr6:108953215 (GRCh38)
Gene constraint: LOEUF 0.936 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.57
Residue 593: 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.Ala593Ser Uncertain significance ★ ⚠ same residue
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.Gly438= Benign same condition
ARMC2 p.Ile630Val Benign same condition
ARMC2 p.Met166Thr Benign same condition
ARMC2 p.Pro622= Likely 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-ala593 (accessed [today's date]).

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