Is ARMC2 p.Ile185Val (c.553A>G) pathogenic?

ARMC2 p.Ile185Val (c.553A>G) is classified Conflicting classifications of pathogenicity in ARMC2 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2024-05-16). AlphaMissense: likely benign (0.0658); Rare (popmax 0.184%, afr); Associated with ARMC2-related disorder.

What condition is associated with ARMC2 p.Ile185Val (c.553A>G)?

ARMC2 p.Ile185Val (c.553A>G) is associated with ARMC2-related disorder (ClinVar).

How common is ARMC2 p.Ile185Val (c.553A>G) in the general population?

ARMC2 p.Ile185Val (c.553A>G) is rare (popmax 0.184%, afr) (gnomAD).

What do computational predictors say about ARMC2 p.Ile185Val (c.553A>G)?

AlphaMissense predicts likely benign (score 0.0658) — an in-silico prediction, not a clinical call.

ARMC2 p.Ile185Val

c.553A>G · rs143895116 · VCV1049935

Conflicting classifications of pathogenicity No assertion criteria

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0658 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.184%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ARMC2-related disorder

Computational evidence

Protein change
AlphaMissense	0.0658	likely benign
REVEL	0.018	moderately benign-leaning
SaProt	LLR -5.54	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.1	GERP -5.2
Regional constraint	o/e 0.89	unconstrained · MANE · 119 kb · p 0.00055 · regional, not allelic
Overall
CADD	0.002	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.184% African / African-American · 138/75,040 alleles

Filtering AF 0.159% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.149%

Overall 0.0126% 204/1,613,012 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.184%	544
East Asian	0.123%	815
Middle Eastern	0.0165%	6,058
Remaining individualsnot grpmax-eligible	0.0064%	15,614
South Asian	0.00331%	30,247
Admixed American	0.00167%	59,870
European (non-Finnish)	0.00017%	589,758

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.Ile185Val
Coding: c.553A>G
MANE Select: NM_032131
dbSNP: rs143895116
Type: single nucleotide variant
Location: chr6:108876232 (GRCh38)
Gene constraint: LOEUF 0.936 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.57
Residue 185: 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 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.Pro622= Likely 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-ile185val (accessed [today's date]).

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