Is DARS1 p.Asp57Glu (c.171T>A) pathogenic?

DARS1 p.Asp57Glu (c.171T>A) is classified Uncertain significance in DARS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-03). AlphaMissense: likely benign (0.1578); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with DARS1 p.Asp57Glu (c.171T>A)?

DARS1 p.Asp57Glu (c.171T>A) is associated with Inborn genetic diseases (ClinVar).

How common is DARS1 p.Asp57Glu (c.171T>A) in the general population?

DARS1 p.Asp57Glu (c.171T>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about DARS1 p.Asp57Glu (c.171T>A)?

AlphaMissense predicts likely benign (score 0.1578) — an in-silico prediction, not a clinical call.

DARS1 p.Asp57Glu

c.171T>A · rs747934762 · VCV3080103

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1578 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1578	likely benign
REVEL	0.298	indeterminate
SaProt	LLR -6.68	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.1	GERP 1.7, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 78 kb · p 0.69 · regional, not allelic
Overall
CADD	20.7	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 0.00167% Admixed American · 1/59,926 alleles

Overall 7.24e-05% 1/1,380,452 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.Asp57Glu
Coding: c.171T>A
MANE Select: NM_001349
dbSNP: rs747934762
Type: single nucleotide variant
Location: chr2:135979320 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DARS1 p.Arg197Cys Uncertain significance ★★ ⚠ same condition
DARS1 p.Arg498Gln Uncertain significance ★★ ⚠ same condition
DARS1 p.Arg63His Uncertain significance ★★ ⚠ same condition
DARS1 p.Asn233Ser Uncertain significance ★★ ⚠ same condition
DARS1 p.Glu357Lys Uncertain significance ★★ ⚠ same condition
DARS1 p.Gly170Arg Uncertain significance ★★ ⚠ same condition
DARS1 p.Gly359Glu Uncertain significance ★★ ⚠ same condition
DARS1 p.His138Arg Uncertain significance ★★ ⚠ same condition

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-asp57glu (accessed [today's date]).

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