Is DARS1 p.Pro162Ser (c.484C>T) pathogenic?

DARS1 p.Pro162Ser (c.484C>T) is classified Conflicting classifications of pathogenicity in DARS1 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-12). AlphaMissense: likely benign (0.1449); Rare (popmax 0.236%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DARS1 p.Pro162Ser (c.484C>T)?

DARS1 p.Pro162Ser (c.484C>T) is associated with Inborn genetic diseases, hypomyelination with brain stem and spinal cord involvement and leg spasticity (ClinVar).

How common is DARS1 p.Pro162Ser (c.484C>T) in the general population?

DARS1 p.Pro162Ser (c.484C>T) is rare (popmax 0.236%, nfe) (gnomAD).

What do computational predictors say about DARS1 p.Pro162Ser (c.484C>T)?

AlphaMissense predicts likely benign (score 0.1449) — an in-silico prediction, not a clinical call.

DARS1 p.Pro162Ser

c.484C>T · rs149170955 · VCV735228

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1449 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.236%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1449	likely benign
REVEL	0.441	indeterminate
SaProt	LLR -6.10	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 12	GERP 1.9, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 78 kb · p 0.69 · regional, not allelic
Overall
CADD	23.2	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 0.236% European (non-Finnish) · 2,788/1,179,460 alleles

Filtering AF 0.229% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.226%

Overall 0.219% 3,537/1,613,328 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.627%	159
European (non-Finnish)grpmax	0.236%	423
Admixed American	0.22%	455
Ashkenazi Jewishnot grpmax-eligible	0.21%	477
Remaining individualsnot grpmax-eligible	0.173%	578
Middle Eastern	0.0825%	1,212
African / African-American	0.0253%	3,949
South Asian	0.0242%	4,137

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro162Ser
Coding: c.484C>T
MANE Select: NM_001349
dbSNP: rs149170955
Type: single nucleotide variant
Location: chr2:135933930 (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

Also linked: hypomyelination with brain stem and spinal cord involvement and leg spasticity

Similar variants

DARS1 p.Pro162Ala Uncertain significance ★ ⚠ same residue
DARS1 p.Arg197Cys Uncertain significance ★★ ⚠ same condition
DARS1 p.Arg498Gln Uncertain significance ★★ ⚠ same condition
DARS1 p.Arg63His Uncertain significance ★★ ⚠ same condition
DARS1 p.Arg81His 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

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-pro162ser (accessed [today's date]).

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