Is ARSG p.Arg95Trp (c.283C>T) pathogenic?

ARSG p.Arg95Trp (c.283C>T) is classified Conflicting classifications of pathogenicity in ARSG (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-10-16). AlphaMissense: likely pathogenic (0.8162); Very rare (popmax 0.00223%, eas).

How common is ARSG p.Arg95Trp (c.283C>T) in the general population?

ARSG p.Arg95Trp (c.283C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about ARSG p.Arg95Trp (c.283C>T)?

AlphaMissense predicts likely pathogenic (score 0.8162) — an in-silico prediction, not a clinical call.

ARSG p.Arg95Trp

c.283C>T · rs1016594361 · VCV934156

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8162 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8162	likely pathogenic
REVEL	0.794	moderately pathogenic-leaning
SaProt	LLR -15.38	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 0.63, phastCons 0.97
Regional constraint	o/e 0.93	unconstrained · MANE · 113 kb · p 0.075 · regional, not allelic
Overall
CADD	25.2	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 0.00223% East Asian · 1/44,882 alleles

Filtering AF 0.000953% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.00137% 20/1,461,780 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,882
Remaining individualsnot grpmax-eligible	0.0016%	62,502
European (non-Finnish)	0.00153%	65,554

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: ARSG
Protein: p.Arg95Trp
Coding: c.283C>T
MANE Select: NM_001267727
dbSNP: rs1016594361
Type: single nucleotide variant
Location: chr17:68343668 (GRCh38)
Gene constraint: LOEUF 0.996 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.90

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

Similar variants

ARSG p.Arg95Gln Uncertain significance ★★ ⚠ same residue
ARSG c.1091+1G>A Likely pathogenic ★★ same type
ARSG c.982+2T>G Likely pathogenic ★★ same type
ARSG p.Ala180Val Uncertain significance ★★ ⚠ same type
ARSG p.Ala262Val Uncertain significance ★★ ⚠ same type
ARSG p.Ala313Val Uncertain significance ★★ ⚠ same type
ARSG p.Ala374Pro Uncertain significance ★★ ⚠ same type
ARSG p.Ala437Val 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/arsg-p-arg95trp (accessed [today's date]).

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