Is ARMC5 p.Arg690Gln (c.2069G>A) pathogenic?

ARMC5 p.Arg690Gln (c.2069G>A) is classified Uncertain significance in ARMC5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-16). AlphaMissense: likely benign (0.073); Ultra-rare (popmax 0.0214%, afr); Associated with ARMC5-related disorder.

What condition is associated with ARMC5 p.Arg690Gln (c.2069G>A)?

ARMC5 p.Arg690Gln (c.2069G>A) is associated with ARMC5-related disorder (ClinVar).

How common is ARMC5 p.Arg690Gln (c.2069G>A) in the general population?

ARMC5 p.Arg690Gln (c.2069G>A) is ultra-rare (popmax 0.0214%, afr) (gnomAD).

What do computational predictors say about ARMC5 p.Arg690Gln (c.2069G>A)?

AlphaMissense predicts likely benign (score 0.073) — an in-silico prediction, not a clinical call.

ARMC5 p.Arg690Gln

c.2069G>A · rs758434668 · VCV2389878

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.073 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0214%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ARMC5-related disorder

Computational evidence

Protein change
AlphaMissense	0.073	likely benign
REVEL	0.06	moderately benign-leaning
SaProt	LLR -2.41	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 2.2	GERP -3.1, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 4,961 bp · p 1.6e-10 · regional, not allelic
Overall
CADD	14.68	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0214% African / African-American · 16/74,800 alleles

Filtering AF 0.0133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0109%

Overall 0.00124% 20/1,606,952 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0214%	4,675
Admixed American	0.00167%	59,976
Remaining individualsnot grpmax-eligible	0.0016%	62,408
South Asian	0.0011%	91,078
European (non-Finnish)	8.48e-05%	1,179,746

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: ARMC5
Protein: p.Arg690Gln
Coding: c.2069G>A
MANE Select: NM_001105247
dbSNP: rs758434668
Type: single nucleotide variant
Location: chr16:31466150 (GRCh38)
Gene constraint: LOEUF 0.772 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.27
Residue 690: a UniProt-annotated variant site (in aimah2; uncertain significance); a UniProt-annotated variant site (in aimah2)

Full ARMC5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ARMC5-related disorder

Similar variants

ARMC5 p.Arg173Ter Pathogenic ★★ same condition
ARMC5 p.Pro606Leu Uncertain significance ★★ ⚠ same condition
ARMC5 p.Arg267Ter Pathogenic ★ same condition
ARMC5 p.Arg315Pro Likely pathogenic ★ same condition
ARMC5 p.Gln759Ter Likely pathogenic ★ same condition
ARMC5 p.Ser107Ter Likely pathogenic ★ same condition
ARMC5 c.1864+168C>T Uncertain significance ★ same condition
ARMC5 c.1864+179C>A Uncertain significance ★ 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/armc5-p-arg690gln (accessed [today's date]).

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