Is ARMC5 p.Thr769= (c.2307C>T) pathogenic?

ARMC5 p.Thr769= (c.2307C>T) is classified Likely benign in ARMC5 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-05-20). Very rare (popmax 0.00933%, afr); Associated with ARMC5-related disorder.

What condition is associated with ARMC5 p.Thr769= (c.2307C>T)?

ARMC5 p.Thr769= (c.2307C>T) is associated with ARMC5-related disorder (ClinVar).

How common is ARMC5 p.Thr769= (c.2307C>T) in the general population?

ARMC5 p.Thr769= (c.2307C>T) is very rare (popmax 0.00933%, afr) (gnomAD).

ARMC5 p.Thr769=

c.2307C>T · rs565794858 · VCV3032372

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00933%, 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 -6.4	GERP -3.4
Overall
CADD	0.301	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00933% African / African-American · 7/75,064 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00308%

Overall 0.00174% 28/1,612,634 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00933%	10,723
East Asian	0.00446%	22,442
Remaining individualsnot grpmax-eligible	0.0016%	62,478
European (non-Finnish)	0.00144%	69,403
South Asian	0.0011%	91,060

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.Thr769=
Coding: c.2307C>T
MANE Select: NM_001105247
dbSNP: rs565794858
Type: single nucleotide variant
Location: chr16:31466388 (GRCh38)
Gene constraint: LOEUF 0.772 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.27
Residue 769: a UniProt-annotated variant site (in aimah2; uncertain significance); a UniProt-annotated variant site (in aimah2); the btb domain

Full ARMC5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ARMC5-related disorder

Similar variants

ARMC5 p.Thr769Ser Uncertain significance ★ ⚠ same residue
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

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-thr769 (accessed [today's date]).

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