Is ARMC5 p.Arg176Cys (c.526C>T) pathogenic?

ARMC5 p.Arg176Cys (c.526C>T) is classified Uncertain significance in ARMC5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-03). AlphaMissense: likely pathogenic (0.8661); Very rare (popmax 0.00445%, eas); Associated with Inborn genetic diseases.

What condition is associated with ARMC5 p.Arg176Cys (c.526C>T)?

ARMC5 p.Arg176Cys (c.526C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ARMC5 p.Arg176Cys (c.526C>T) in the general population?

ARMC5 p.Arg176Cys (c.526C>T) is very rare (popmax 0.00445%, eas) (gnomAD).

What do computational predictors say about ARMC5 p.Arg176Cys (c.526C>T)?

AlphaMissense predicts likely pathogenic (score 0.8661) — an in-silico prediction, not a clinical call.

ARMC5 p.Arg176Cys

c.526C>T · VCV4146902

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8661 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00445%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8661	likely pathogenic
REVEL	0.382	indeterminate
SaProt	LLR -9.34	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 4,961 bp · p 1.6e-10 · regional, not allelic
Overall
CADD	30.0	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 0.00445% East Asian · 2/44,896 alleles

Filtering AF 0.00259% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00233%

Overall 0.00279% 45/1,614,088 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00445%	22,448
European (non-Finnish)	0.00347%	28,781
Admixed American	0.00167%	60,012
South Asian	0.0011%	91,088

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.Arg176Cys
Coding: c.526C>T
MANE Select: NM_001105247
Type: single nucleotide variant
Location: chr16:31461972 (GRCh38)
Gene constraint: LOEUF 0.772 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.27
Residue 176: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ARMC5 p.Ala55Val Uncertain significance ★★ ⚠ same condition
ARMC5 p.Arg611Leu Uncertain significance ★★ ⚠ same condition
ARMC5 p.Ser266Thr Uncertain significance ★★ ⚠ same condition
ARMC5 p.Trp801Cys Uncertain significance ★★ ⚠ same condition
ARMC5 p.Ala100Thr Uncertain significance ★ ⚠ same condition
ARMC5 p.Ala206Ser Uncertain significance ★ ⚠ same condition
ARMC5 p.Ala22Val Uncertain significance ★ ⚠ same condition
ARMC5 p.Ala243Gly 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-arg176cys (accessed [today's date]).

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