Is AARSD1 p.Asn331Ser (c.992A>G) pathogenic?

AARSD1 p.Asn331Ser (c.992A>G) is classified Uncertain significance in AARSD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-12). AlphaMissense: likely benign (0.094); Ultra-rare (popmax 0.02%, eas).

How common is AARSD1 p.Asn331Ser (c.992A>G) in the general population?

AARSD1 p.Asn331Ser (c.992A>G) is ultra-rare (popmax 0.02%, eas) (gnomAD).

What do computational predictors say about AARSD1 p.Asn331Ser (c.992A>G)?

AlphaMissense predicts likely benign (score 0.094) — an in-silico prediction, not a clinical call.

AARSD1 p.Asn331Ser

c.992A>G · rs758557782 · VCV2317861

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.094 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.094	likely benign
REVEL	0.114	moderately benign-leaning
SaProt	LLR -6.56	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 3.4	GERP 2.1, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 14 kb · p 0.6 · regional, not allelic
Overall
CADD	22.9	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 0.02% East Asian · 9/44,896 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00779%

Overall 0.00105% 17/1,614,016 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.02%	4,988
South Asian	0.00329%	30,361
Admixed American	0.00167%	59,990
European (non-Finnish)	0.000339%	295,004

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: AARSD1
Protein: p.Asn331Ser
Coding: c.992A>G
MANE Select: NM_001261434
dbSNP: rs758557782
Type: single nucleotide variant
Location: chr17:42953740 (GRCh38)
Gene constraint: LOEUF 1.122 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.77

Full AARSD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AARSD1 p.Ala24Pro Uncertain significance ★ ⚠ same type
AARSD1 p.Ala24Val Uncertain significance ★ ⚠ same type
AARSD1 p.Ala262Val Uncertain significance ★ ⚠ same type
AARSD1 p.Ala360Val Uncertain significance ★ ⚠ same type
AARSD1 p.Ala399Val Uncertain significance ★ ⚠ same type
AARSD1 p.Arg101Gln Uncertain significance ★ ⚠ same type
AARSD1 p.Arg165Trp Uncertain significance ★ ⚠ same type
AARSD1 p.Arg186Gln Uncertain significance ★ 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/aarsd1-p-asn331ser (accessed [today's date]).

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