Is AARS1 p.Ser864= (c.2592C>T) pathogenic?

AARS1 p.Ser864= (c.2592C>T) is classified Benign/Likely benign in AARS1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-13). Rare (popmax 0.134%, eas); Associated with Charcot-Marie-Tooth disease type 2.

What condition is associated with AARS1 p.Ser864= (c.2592C>T)?

AARS1 p.Ser864= (c.2592C>T) is associated with Charcot-Marie-Tooth disease type 2, Charcot-Marie-Tooth disease axonal type 2N (ClinVar).

How common is AARS1 p.Ser864= (c.2592C>T) in the general population?

AARS1 p.Ser864= (c.2592C>T) is rare (popmax 0.134%, eas) (gnomAD).

AARS1 p.Ser864=

c.2592C>T · rs11537665 · VCV700156

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.134%, eas)

Conditions

Charcot-Marie-Tooth disease type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP -4.5	GERP -2.8
Overall
CADD	10.47	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.134% East Asian · 60/44,888 alleles

Filtering AF 0.107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0967%

Overall 0.00768% 124/1,613,902 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.134%	748
Ashkenazi Jewishnot grpmax-eligible	0.101%	987
Admixed American	0.00833%	12,006
Remaining individualsnot grpmax-eligible	0.0064%	15,626
European (non-Finnish)	0.00203%	49,167
South Asian	0.0011%	91,084

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: AARS1
Protein: p.Ser864=
Coding: c.2592C>T
MANE Select: NM_001605
dbSNP: rs11537665
Type: single nucleotide variant
Location: chr16:70253729 (GRCh38)
Gene constraint: LOEUF 0.772 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 90.66 · 10 PDB

Full AARS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Charcot-Marie-Tooth disease type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Charcot-Marie-Tooth disease axonal type 2N

Similar variants

AARS1 p.Ser864Asn Uncertain significance ★ ⚠ same residue
AARS1 c.2177+1G>A Pathogenic/Likely pathogenic ★★ same condition
AARS1 p.Arg13Ter Pathogenic ★★ same condition
AARS1 p.Arg246Ter Pathogenic/Likely pathogenic ★★ same condition
AARS1 p.Arg329Cys Likely pathogenic ★★ same condition
AARS1 p.Arg329His Pathogenic/Likely pathogenic ★★ same condition
AARS1 p.Arg330Ter Pathogenic/Likely pathogenic ★★ same condition
AARS1 p.Arg333Ter Pathogenic/Likely pathogenic ★★ 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/aars1-p-ser864 (accessed [today's date]).

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