Is ART1 p.Arg102Cys (c.304C>T) pathogenic?

ART1 p.Arg102Cys (c.304C>T) is classified Uncertain significance in ART1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-08). AlphaMissense: likely benign (0.1289); Very rare (popmax 0.00669%, eas).

How common is ART1 p.Arg102Cys (c.304C>T) in the general population?

ART1 p.Arg102Cys (c.304C>T) is very rare (popmax 0.00669%, eas) (gnomAD).

What do computational predictors say about ART1 p.Arg102Cys (c.304C>T)?

AlphaMissense predicts likely benign (score 0.1289) — an in-silico prediction, not a clinical call.

ART1 p.Arg102Cys

c.304C>T · VCV3787802

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1289 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1289	likely benign
REVEL	0.091	moderately benign-leaning
SaProt	LLR -10.02	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 -0.69	GERP -3
Regional constraint	o/e 1.13	unconstrained · MANE · 4,972 bp · p 0.0056 · regional, not allelic
Overall
CADD	17.72	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 0.00669% East Asian · 3/44,872 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.00118% 19/1,611,682 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,957
South Asian	0.0022%	45,448
Remaining individualsnot grpmax-eligible	0.0016%	62,406
European (non-Finnish)	0.0011%	90,716

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.Arg102Cys
Coding: c.304C>T
MANE Select: NM_004314
Type: single nucleotide variant
Location: chr11:3659823 (GRCh38)
Gene constraint: LOEUF 1.476 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.03
Residue 102: 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.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
ART1 p.Ala227Ser 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-arg102cys (accessed [today's date]).

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