Is DARS1 p.Leu152= (c.456G>T) pathogenic?

DARS1 p.Leu152= (c.456G>T) is classified Likely benign in DARS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-19). Very rare (popmax 0.000339%, nfe).

How common is DARS1 p.Leu152= (c.456G>T) in the general population?

DARS1 p.Leu152= (c.456G>T) is very rare (popmax 0.000339%, nfe) (gnomAD).

DARS1 p.Leu152=

c.456G>T · rs1575391182 · VCV1682561

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.25	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -0.004	GERP 1.9, phastCons 0.77
Overall
CADD	6.669	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,742 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000274% 4/1,461,486 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: DARS1
Protein: p.Leu152=
Coding: c.456G>T
MANE Select: NM_001349
dbSNP: rs1575391182
Type: single nucleotide variant
Location: chr2:135933958 (GRCh38)
Gene constraint: LOEUF 1.023 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.69 · 3 PDB

Full DARS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DARS1 p.Ala429Thr Uncertain significance ★★ ⚠ same type
DARS1 p.Arg197Cys Uncertain significance ★★ ⚠ same type
DARS1 p.Arg498Gln Uncertain significance ★★ ⚠ same type
DARS1 p.Arg63His Uncertain significance ★★ ⚠ same type
DARS1 p.Arg81His Uncertain significance ★★ ⚠ same type
DARS1 p.Asn233Ser Uncertain significance ★★ ⚠ same type
DARS1 p.Glu357Lys Uncertain significance ★★ ⚠ same type
DARS1 p.Gly170Arg 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/dars1-p-leu152 (accessed [today's date]).

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