Is DARS1 p.Asp19= (c.57C>T) pathogenic?

DARS1 p.Asp19= (c.57C>T) is classified Likely benign in DARS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-02). Ultra-rare (popmax 0.0356%, eas).

How common is DARS1 p.Asp19= (c.57C>T) in the general population?

DARS1 p.Asp19= (c.57C>T) is ultra-rare (popmax 0.0356%, eas) (gnomAD).

DARS1 p.Asp19=

c.57C>T · VCV4700052

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0356%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.62	GERP -1.5, phastCons 1
Overall
CADD	14.44	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0356% East Asian · 16/44,886 alleles

Filtering AF 0.0223% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0182%

Overall 0.00167% 27/1,613,724 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0356%	2,805
European (non-Finnish)	0.000932%	107,267

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.Asp19=
Coding: c.57C>T
MANE Select: NM_001349
Type: single nucleotide variant
Location: chr2:135985412 (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-asp19 (accessed [today's date]).

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