Is PUS3 p.Arg140= (c.420G>A) pathogenic?

PUS3 p.Arg140= (c.420G>A) is classified Likely benign in PUS3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-05). Very rare (popmax 0.00892%, eas).

How common is PUS3 p.Arg140= (c.420G>A) in the general population?

PUS3 p.Arg140= (c.420G>A) is very rare (popmax 0.00892%, eas) (gnomAD).

PUS3 p.Arg140=

c.420G>A · rs1944563682 · VCV1619204

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00892%, eas)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.71	GERP -3.5
Overall
CADD	2.238	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00892% East Asian · 4/44,868 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000249% 4/1,609,168 alleles · very rare exomes 4/1,456,834 · genomes 0/152,334 · joint denominator

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: PUS3
Protein: p.Arg140=
Coding: c.420G>A
MANE Select: NM_031307
dbSNP: rs1944563682
Type: single nucleotide variant
Location: chr11:125895748 (GRCh38)

Full PUS3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/pus3-p-arg140 (accessed [today's date]).

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