Is ARMC5 p.Ala582Val (c.1745C>T) pathogenic?

ARMC5 p.Ala582Val (c.1745C>T) is classified Uncertain significance in ARMC5 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-05-14). AlphaMissense: likely pathogenic (0.6206); Absent from gnomAD v4.1; Associated with ARMC5-related disorder.

What condition is associated with ARMC5 p.Ala582Val (c.1745C>T)?

ARMC5 p.Ala582Val (c.1745C>T) is associated with ARMC5-related disorder (ClinVar).

How common is ARMC5 p.Ala582Val (c.1745C>T) in the general population?

ARMC5 p.Ala582Val (c.1745C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARMC5 p.Ala582Val (c.1745C>T)?

AlphaMissense predicts likely pathogenic (score 0.6206) — an in-silico prediction, not a clinical call.

ARMC5 p.Ala582Val

c.1745C>T · VCV3347080

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6206 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,599,230)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ARMC5-related disorder

Computational evidence

Protein change
AlphaMissense	0.6206	likely pathogenic
REVEL	0.153	moderately benign-leaning
SaProt	LLR -9.84	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 4,961 bp · p 1.6e-10 · regional, not allelic
Overall
CADD	24.3	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

No allele count reported in gnomAD v4.1 (AN 1,599,230). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ARMC5
Protein: p.Ala582Val
Coding: c.1745C>T
MANE Select: NM_001105247
Type: single nucleotide variant
Location: chr16:31464768 (GRCh38)
Gene constraint: LOEUF 0.772 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.27
Residue 582: 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.Arg690Gln Uncertain significance ★★ ⚠ 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

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-ala582val (accessed [today's date]).

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