Is AARSD1 p.Arg393Trp (c.1177C>T) pathogenic?

AARSD1 p.Arg393Trp (c.1177C>T) is classified Uncertain significance in AARSD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-01). AlphaMissense: likely benign (0.2407); Ultra-rare (popmax 0.0108%, nfe).

How common is AARSD1 p.Arg393Trp (c.1177C>T) in the general population?

AARSD1 p.Arg393Trp (c.1177C>T) is ultra-rare (popmax 0.0108%, nfe) (gnomAD).

What do computational predictors say about AARSD1 p.Arg393Trp (c.1177C>T)?

AlphaMissense predicts likely benign (score 0.2407) — an in-silico prediction, not a clinical call.

AARSD1 p.Arg393Trp

c.1177C>T · rs371371802 · VCV2385457

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2407 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0108%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2407	likely benign
REVEL	0.227	benign-leaning
SaProt	LLR -12.47	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.1	GERP 0.99, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 14 kb · p 0.6 · regional, not allelic
Overall
CADD	29.0	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 0.0108% European (non-Finnish) · 128/1,179,986 alleles

Filtering AF 0.00928% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00871%

Overall 0.00836% 135/1,613,960 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0108%	9,219
Remaining individualsnot grpmax-eligible	0.0048%	20,834
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
African / African-American	0.00267%	37,503
Admixed American	0.00167%	59,990

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.Arg393Trp
Coding: c.1177C>T
MANE Select: NM_001261434
dbSNP: rs371371802
Type: single nucleotide variant
Location: chr17:42950655 (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-arg393trp (accessed [today's date]).

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