Is ARMC2 p.Arg142Trp (c.424C>T) pathogenic?

ARMC2 p.Arg142Trp (c.424C>T) is classified Uncertain significance in ARMC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-01). AlphaMissense: likely benign (0.1455); Ultra-rare (popmax 0.0245%, eas).

How common is ARMC2 p.Arg142Trp (c.424C>T) in the general population?

ARMC2 p.Arg142Trp (c.424C>T) is ultra-rare (popmax 0.0245%, eas) (gnomAD).

What do computational predictors say about ARMC2 p.Arg142Trp (c.424C>T)?

AlphaMissense predicts likely benign (score 0.1455) — an in-silico prediction, not a clinical call.

ARMC2 p.Arg142Trp

c.424C>T · VCV3430762

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1455 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0245%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1455	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	LLR -10.72	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 1.4, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 119 kb · p 0.00055 · regional, not allelic
Overall
CADD	25.3	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 0.0245% East Asian · 11/44,886 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.0062% 100/1,613,634 alleles · ultra-rare exomes 95/1,461,448 · genomes 5/152,186 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0245%	4,081
Admixed American	0.0167%	5,997
European (non-Finnish)	0.0061%	16,386
Remaining individualsnot grpmax-eligible	0.0048%	20,817
South Asian	0.00439%	22,759

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: ARMC2
Protein: p.Arg142Trp
Coding: c.424C>T
MANE Select: NM_032131
Type: single nucleotide variant
Location: chr6:108868956 (GRCh38)
Gene constraint: LOEUF 0.936 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.57
Residue 142: a UniProt-annotated variant site (in spgf38; uncertain significance)

Full ARMC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARMC2 p.Arg142Gln Uncertain significance ★ ⚠ same residue
ARMC2 c.2153-1G>C Likely pathogenic ★ same type
ARMC2 p.Asn743Asp Likely pathogenic ★ same type
ARMC2 p.Ala123Val Uncertain significance ★ ⚠ same type
ARMC2 p.Ala143Thr Uncertain significance ★ ⚠ same type
ARMC2 p.Ala231Thr Uncertain significance ★ ⚠ same type
ARMC2 p.Ala260Pro Uncertain significance ★ ⚠ same type
ARMC2 p.Ala292Asp 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/armc2-p-arg142trp (accessed [today's date]).

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