Is ARMC5 p.Pro7= (c.21A>C) pathogenic?

ARMC5 p.Pro7= (c.21A>C) is classified Likely benign in ARMC5 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-02-01). Very rare (popmax 0.00061%, nfe); Associated with ARMC5-related disorder.

What condition is associated with ARMC5 p.Pro7= (c.21A>C)?

ARMC5 p.Pro7= (c.21A>C) is associated with ARMC5-related disorder (ClinVar).

How common is ARMC5 p.Pro7= (c.21A>C) in the general population?

ARMC5 p.Pro7= (c.21A>C) is very rare (popmax 0.00061%, nfe) (gnomAD).

ARMC5 p.Pro7=

c.21A>C · rs1473909978 · VCV3028967

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00061%, nfe)

Conditions

ARMC5-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 -0.14	GERP -4.5
Overall
CADD	1.642	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00061% European (non-Finnish) · 7/1,146,770 alleles

Filtering AF 0.000254% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000163%

Overall 0.000456% 7/1,534,936 alleles · very rare

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.Pro7=
Coding: c.21A>C
MANE Select: NM_001105247 · reported on NM_001301820
dbSNP: rs1473909978
Type: single nucleotide variant
Location: chr16:31459322 (GRCh38)
Gene constraint: LOEUF 0.772 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.27

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-pro7 (accessed [today's date]).

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