Is AARS1 p.Ala78Ser (c.232G>T) pathogenic?

AARS1 p.Ala78Ser (c.232G>T) is classified Uncertain significance in AARS1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-10-30). AlphaMissense: likely pathogenic (0.8796); Very rare (popmax 0.00445%, eas); Associated with Inborn genetic diseases.

What condition is associated with AARS1 p.Ala78Ser (c.232G>T)?

AARS1 p.Ala78Ser (c.232G>T) is associated with Inborn genetic diseases, developmental and epileptic encephalopathy, 29, Charcot-Marie-Tooth disease type 2 (ClinVar).

How common is AARS1 p.Ala78Ser (c.232G>T) in the general population?

AARS1 p.Ala78Ser (c.232G>T) is very rare (popmax 0.00445%, eas) (gnomAD).

What do computational predictors say about AARS1 p.Ala78Ser (c.232G>T)?

AlphaMissense predicts likely pathogenic (score 0.8796) — an in-silico prediction, not a clinical call.

AARS1 p.Ala78Ser

c.232G>T · rs1387945918 · VCV2441640

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.8796 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00445%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8796	likely pathogenic
REVEL	0.758	pathogenic-leaning
SaProt	LLR -9.35	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 30 kb · p 0.25 · regional, not allelic
Overall
CADD	28.4	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 0.00445% East Asian · 2/44,900 alleles

Filtering AF 0.000738% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000186% 3/1,614,024 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00445%	22,450
Remaining individualsnot grpmax-eligible	0.0016%	62,484

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.Ala78Ser
Coding: c.232G>T
MANE Select: NM_001605
dbSNP: rs1387945918
Type: single nucleotide variant
Location: chr16:70277067 (GRCh38)
Gene constraint: LOEUF 0.772 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 90.66 · 10 PDB
Residue 78: a β-strand

Full AARS1 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: developmental and epileptic encephalopathy, 29 Charcot-Marie-Tooth disease type 2

Similar variants

AARS1 p.Ala78Thr 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-ala78ser (accessed [today's date]).

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