Is ARMC3 p.Arg599Trp (c.1795C>T) pathogenic?

ARMC3 p.Arg599Trp (c.1795C>T) is classified Uncertain significance in ARMC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-02). AlphaMissense: likely benign (0.2647); Ultra-rare (popmax 0.0192%, nfe).

How common is ARMC3 p.Arg599Trp (c.1795C>T) in the general population?

ARMC3 p.Arg599Trp (c.1795C>T) is ultra-rare (popmax 0.0192%, nfe) (gnomAD).

What do computational predictors say about ARMC3 p.Arg599Trp (c.1795C>T)?

AlphaMissense predicts likely benign (score 0.2647) — an in-silico prediction, not a clinical call.

ARMC3 p.Arg599Trp

c.1795C>T · VCV4146771

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2647 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0192%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2647	likely benign
REVEL	0.334	indeterminate
SaProt	LLR -11.45	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	Δ0.25	donor loss · deltas
Pangolin	Δ0.35	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 105 kb · p 0.0086 · regional, not allelic
Overall
CADD	29.5	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 0.0192% European (non-Finnish) · 227/1,179,644 alleles

Filtering AF 0.0172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0163%

Overall 0.0163% 263/1,613,150 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0192%	5,197
Remaining individualsnot grpmax-eligible	0.0192%	5,205
East Asian	0.0134%	7,478
African / African-American	0.012%	8,330
Admixed American	0.00669%	14,955
South Asian	0.0055%	18,183

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: ARMC3
Protein: p.Arg599Trp
Coding: c.1795C>T
MANE Select: NM_173081
Type: single nucleotide variant
Location: chr10:23006947 (GRCh38)
Gene constraint: LOEUF 0.91 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.81

Full ARMC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARMC3 p.Arg599Gln Uncertain significance ★ ⚠ same residue
ARMC3 p.Met441Ile Uncertain significance ★★ ⚠ same type
ARMC3 c.916+1G>A Uncertain significance ★ same type
ARMC3 p.Ala115Asp Uncertain significance ★ ⚠ same type
ARMC3 p.Ala118Thr Uncertain significance ★ ⚠ same type
ARMC3 p.Ala138Ser Uncertain significance ★ ⚠ same type
ARMC3 p.Ala192Ser Uncertain significance ★ ⚠ same type
ARMC3 p.Ala211Val Uncertain significance ★ ⚠ 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/armc3-p-arg599trp (accessed [today's date]).

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