Is ART1 p.Leu205Val (c.613C>G) pathogenic?

ART1 p.Leu205Val (c.613C>G) is classified Uncertain significance in ART1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-21). AlphaMissense: likely benign (0.1252); Very rare (popmax 0.000763%, nfe).

How common is ART1 p.Leu205Val (c.613C>G) in the general population?

ART1 p.Leu205Val (c.613C>G) is very rare (popmax 0.000763%, nfe) (gnomAD).

What do computational predictors say about ART1 p.Leu205Val (c.613C>G)?

AlphaMissense predicts likely benign (score 0.1252) — an in-silico prediction, not a clinical call.

ART1 p.Leu205Val

c.613C>G · VCV4149951

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1252 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000763%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1252	likely benign
REVEL	0.132	moderately benign-leaning
SaProt	LLR -9.17	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.81	GERP -3, phastCons 0.97
Regional constraint	o/e 1.13	unconstrained · MANE · 4,972 bp · p 0.0056 · regional, not allelic
Overall
CADD	17.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000763% European (non-Finnish) · 9/1,180,018 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000558% 9/1,613,820 alleles · very rare

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.Leu205Val
Coding: c.613C>G
MANE Select: NM_004314
Type: single nucleotide variant
Location: chr11:3660132 (GRCh38)
Gene constraint: LOEUF 1.476 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.03
Residue 205: 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-leu205val (accessed [today's date]).

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