Is DARS2 p.Asp560Ala (c.1679A>C) pathogenic?

DARS2 p.Asp560Ala (c.1679A>C) is classified Uncertain significance in DARS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-02). AlphaMissense: likely pathogenic (0.6601); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DARS2 p.Asp560Ala (c.1679A>C)?

DARS2 p.Asp560Ala (c.1679A>C) is associated with Inborn genetic diseases (ClinVar).

How common is DARS2 p.Asp560Ala (c.1679A>C) in the general population?

DARS2 p.Asp560Ala (c.1679A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DARS2 p.Asp560Ala (c.1679A>C)?

AlphaMissense predicts likely pathogenic (score 0.6601) — an in-silico prediction, not a clinical call.

DARS2 p.Asp560Ala

c.1679A>C · VCV3499710

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6601 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6601	likely pathogenic
REVEL	0.687	pathogenic-leaning
SaProt	LLR -13.35	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 32 kb · p 0.00036 · regional, not allelic
Overall
CADD	29.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DARS2
Protein: p.Asp560Ala
Coding: c.1679A>C
MANE Select: NM_018122
Type: single nucleotide variant
Location: chr1:173856670 (GRCh38)
Gene constraint: LOEUF 0.923 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.91 · 1 PDB
Residue 560: a UniProt-annotated variant site (in lbsl)

Full DARS2 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

DARS2 p.Asp560Val Uncertain significance ★ ⚠ same residue
DARS2 p.Arg58Gly Pathogenic/Likely pathogenic ★★ ⚠ same condition
DARS2 p.Ala554Thr Uncertain significance ★★ ⚠ same condition
DARS2 p.Arg31Gly Uncertain significance ★★ ⚠ same condition
DARS2 p.Arg381Met Uncertain significance ★★ ⚠ same condition
DARS2 p.Asn416Asp Uncertain significance ★★ ⚠ same condition
DARS2 p.Cys590Arg Uncertain significance ★★ ⚠ same condition
DARS2 p.Leu201Phe 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/dars2-p-asp560ala (accessed [today's date]).

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