Is ARMC5 p.Val724= (c.2172C>T) pathogenic?

ARMC5 p.Val724= (c.2172C>T) is classified Likely benign in ARMC5 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-05-24). Ultra-rare (popmax 0.024%, afr); Associated with ARMC5-related disorder.

What condition is associated with ARMC5 p.Val724= (c.2172C>T)?

ARMC5 p.Val724= (c.2172C>T) is associated with ARMC5-related disorder (ClinVar).

How common is ARMC5 p.Val724= (c.2172C>T) in the general population?

ARMC5 p.Val724= (c.2172C>T) is ultra-rare (popmax 0.024%, afr) (gnomAD).

ARMC5 p.Val724=

c.2172C>T · rs759575674 · VCV3048976

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.024%, afr)

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 -1.7	GERP -3.4
Overall
CADD	0.188	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.024% African / African-American · 18/74,926 alleles

Filtering AF 0.0155% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0128%

Overall 0.00112% 18/1,613,760 alleles · ultra-rare exomes 6/1,461,576 · genomes 12/152,184 · joint denominator

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.Val724=
Coding: c.2172C>T
MANE Select: NM_001105247
dbSNP: rs759575674
Type: single nucleotide variant
Location: chr16:31466253 (GRCh38)
Gene constraint: LOEUF 0.772 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.27
Residue 724: 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-val724 (accessed [today's date]).

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