ARMC5 p.Pro748=
c.2244C>T · VCV3352143
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0266%, nfe)
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 -6.3 | GERP -3.4 |
| Overall | ||
| CADD | 4.769 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0266%
European (non-Finnish) · 314/1,179,896 alleles
Filtering AF
0.0242%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0232%
Overall
0.0218%
351/1,613,674 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0266% | 3,758 |
| Remaining individualsnot grpmax-eligible | 0.0208% | 4,805 |
| Admixed American | 0.015% | 6,667 |
| South Asian | 0.0121% | 8,281 |
| Finnishnot grpmax-eligible | 0.00314% | 31,889 |
| African / African-American | 0.00267% | 37,470 |
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.Pro748=
- Coding
- c.2244C>T
- MANE Select
- NM_001105247
- Type
- single nucleotide variant
- Location
- chr16:31466325 (GRCh38)
- Gene constraint
- LOEUF 0.772 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.27
- Residue 748
- a UniProt-annotated variant site (in aimah2; uncertain significance); a UniProt-annotated variant site (in aimah2); the btb domain
Similar variants
- ARMC5 p.Arg173Ter Pathogenic ★★ same type
- ARMC5 p.Ala55Val Uncertain significance ★★ ⚠ same type
- ARMC5 p.Arg611Leu Uncertain significance ★★ ⚠ same type
- ARMC5 p.Arg690Gln Uncertain significance ★★ ⚠ same type
- ARMC5 p.Pro606Leu Uncertain significance ★★ ⚠ same type
- ARMC5 p.Ser266Thr Uncertain significance ★★ ⚠ same type
- ARMC5 p.Trp801Cys Uncertain significance ★★ ⚠ same type
- ARMC5 p.Ala110Thr Benign/Likely benign ★★ same type
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-pro748 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown