Is ARMC5 p.Ala658Val (c.1973C>T) pathogenic?

ARMC5 p.Ala658Val (c.1973C>T) is classified Uncertain significance in ARMC5 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-01-25). AlphaMissense: likely pathogenic (0.5761); Very rare (popmax 0.00329%, sas); Associated with ARMC5-related disorder.

What condition is associated with ARMC5 p.Ala658Val (c.1973C>T)?

ARMC5 p.Ala658Val (c.1973C>T) is associated with ARMC5-related disorder (ClinVar).

How common is ARMC5 p.Ala658Val (c.1973C>T) in the general population?

ARMC5 p.Ala658Val (c.1973C>T) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about ARMC5 p.Ala658Val (c.1973C>T)?

AlphaMissense predicts likely pathogenic (score 0.5761) — an in-silico prediction, not a clinical call.

ARMC5 p.Ala658Val

c.1973C>T · rs1401837338 · VCV3032211

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5761 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ARMC5-related disorder

Computational evidence

Protein change
AlphaMissense	0.5761	likely pathogenic
REVEL	0.191	benign-leaning
SaProt	LLR -8.42	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 0.49, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 4,961 bp · p 1.6e-10 · regional, not allelic
Overall
CADD	25.0	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 0.00329% South Asian · 3/91,058 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.00106% 17/1,605,152 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,353
Finnishnot grpmax-eligible	0.00179%	55,982
European (non-Finnish)	0.0011%	90,734

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.Ala658Val
Coding: c.1973C>T
MANE Select: NM_001105247
dbSNP: rs1401837338
Type: single nucleotide variant
Location: chr16:31465958 (GRCh38)
Gene constraint: LOEUF 0.772 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.27
Residue 658: 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-ala658val (accessed [today's date]).

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