Is AARS1 p.Ala736Val (c.2207C>T) pathogenic?

AARS1 p.Ala736Val (c.2207C>T) is classified Uncertain significance in AARS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2015-10-27). AlphaMissense: likely benign (0.1036); Very rare (popmax 0.000657%).

How common is AARS1 p.Ala736Val (c.2207C>T) in the general population?

AARS1 p.Ala736Val (c.2207C>T) is very rare (popmax 0.000657%) (gnomAD).

What do computational predictors say about AARS1 p.Ala736Val (c.2207C>T)?

AlphaMissense predicts likely benign (score 0.1036) — an in-silico prediction, not a clinical call.

AARS1 p.Ala736Val

c.2207C>T · rs879254073 · VCV246064

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1036 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000657%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1036	likely benign
REVEL	0.103	moderately benign-leaning
SaProt	LLR -6.46	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 8.5	GERP 1.7, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 30 kb · p 0.25 · regional, not allelic
Overall
CADD	20.7	PHRED · no single calibrated threshold — expert panels disagree

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

Grpmax group 0.000657%

Overall 0.000657% 1/152,186 alleles · very rare

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.Ala736Val
Coding: c.2207C>T
MANE Select: NM_001605
dbSNP: rs879254073
Type: single nucleotide variant
Location: chr16:70255807 (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

Similar variants

AARS1 c.2177+1G>A Pathogenic/Likely pathogenic ★★ same type
AARS1 p.Arg13Ter Pathogenic ★★ same type
AARS1 p.Arg246Ter Pathogenic/Likely pathogenic ★★ same type
AARS1 p.Arg329Cys Likely pathogenic ★★ same type
AARS1 p.Arg329His Pathogenic/Likely pathogenic ★★ same type
AARS1 p.Arg330Ter Pathogenic/Likely pathogenic ★★ same type
AARS1 p.Arg333Ter Pathogenic/Likely pathogenic ★★ same type
AARS1 p.Arg598Ter Pathogenic/Likely pathogenic ★★ same type

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-ala736val (accessed [today's date]).

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