Is ART1 p.Arg142Trp (c.424C>T) pathogenic?

ART1 p.Arg142Trp (c.424C>T) is classified Uncertain significance in ART1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-02). AlphaMissense: likely benign (0.1743); Rare (popmax 0.115%, mid).

How common is ART1 p.Arg142Trp (c.424C>T) in the general population?

ART1 p.Arg142Trp (c.424C>T) is rare (popmax 0.115%, mid) (gnomAD).

What do computational predictors say about ART1 p.Arg142Trp (c.424C>T)?

AlphaMissense predicts likely benign (score 0.1743) — an in-silico prediction, not a clinical call.

ART1 p.Arg142Trp

c.424C>T · VCV3316716

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1743 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.115%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1743	likely benign
REVEL	0.19	benign-leaning
SaProt	LLR -11.22	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 1.5	GERP 1.9, phastCons 0.82
Regional constraint	o/e 1.13	unconstrained · MANE · 4,972 bp · p 0.0056 · regional, not allelic
Overall
CADD	24.0	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 0.115% Middle Eastern · 7/6,062 alleles

Filtering AF 0.0542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0384%

Overall 0.00459% 74/1,613,740 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.115%	866
Remaining individualsnot grpmax-eligible	0.0144%	6,943
South Asian	0.00769%	13,005
East Asian	0.00446%	22,441
European (non-Finnish)	0.00398%	25,104
Admixed American	0.00167%	60,024
African / African-American	0.00133%	75,068

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: ART1
Protein: p.Arg142Trp
Coding: c.424C>T
MANE Select: NM_004314
Type: single nucleotide variant
Location: chr11:3659943 (GRCh38)
Gene constraint: LOEUF 1.476 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.03
Residue 142: a disulfide bond; the tr mart core domain

Full ART1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ART1 p.Arg142Gln Uncertain significance ★ ⚠ same residue
ART1 p.Arg140= Benign ★★ same type
ART1 p.Leu43= Benign ★★ same type
ART1 p.Ala120Pro Uncertain significance ★ ⚠ same type
ART1 p.Ala133Val Uncertain significance ★ ⚠ same type
ART1 p.Ala138Val Uncertain significance ★ ⚠ same type
ART1 p.Ala161Ser Uncertain significance ★ ⚠ same type
ART1 p.Ala227Gly 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/art1-p-arg142trp (accessed [today's date]).

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