Is DARS2 p.Asp87Gly (c.260A>G) pathogenic?

DARS2 p.Asp87Gly (c.260A>G) is classified Conflicting classifications of pathogenicity in DARS2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-10-10). AlphaMissense: likely benign (0.1119); Rare (popmax 0.156%, eas); Associated with Inborn genetic diseases.

What condition is associated with DARS2 p.Asp87Gly (c.260A>G)?

DARS2 p.Asp87Gly (c.260A>G) is associated with Inborn genetic diseases (ClinVar).

How common is DARS2 p.Asp87Gly (c.260A>G) in the general population?

DARS2 p.Asp87Gly (c.260A>G) is rare (popmax 0.156%, eas) (gnomAD).

What do computational predictors say about DARS2 p.Asp87Gly (c.260A>G)?

AlphaMissense predicts likely benign (score 0.1119) — an in-silico prediction, not a clinical call.

DARS2 p.Asp87Gly

c.260A>G · rs149598381 · VCV1463639

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1119 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.156%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1119	likely benign
REVEL	0.076	moderately benign-leaning
SaProt	LLR -4.24	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 8.1	GERP 1.8, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 32 kb · p 0.00036 · regional, not allelic
Overall
CADD	21.1	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.156% East Asian · 51/32,752 alleles

Filtering AF 0.122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.109%

Overall 0.0113% 167/1,482,724 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.156%	642
Finnishnot grpmax-eligible	0.0719%	1,390
Remaining individualsnot grpmax-eligible	0.026%	3,846
Middle Eastern	0.0188%	5,312
South Asian	0.00896%	11,155
European (non-Finnish)	0.00492%	20,340
African / African-American	0.00142%	70,578

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: DARS2
Protein: p.Asp87Gly
Coding: c.260A>G
MANE Select: NM_018122
dbSNP: rs149598381
Type: single nucleotide variant
Location: chr1:173828365 (GRCh38)
Gene constraint: LOEUF 0.923 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.91 · 1 PDB

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.Asp87= Conflicting classifications of pathogenicity ★ same residue
DARS2 p.Asp87Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
DARS2 p.Asp87Tyr 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

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-asp87gly (accessed [today's date]).

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