Is PUS3 p.Ser315= (c.945T>C) pathogenic?

PUS3 p.Ser315= (c.945T>C) is classified Likely benign in PUS3 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-06-07). Ultra-rare (popmax 0.0358%, eas); Associated with Inborn genetic diseases.

What condition is associated with PUS3 p.Ser315= (c.945T>C)?

PUS3 p.Ser315= (c.945T>C) is associated with Inborn genetic diseases (ClinVar).

How common is PUS3 p.Ser315= (c.945T>C) in the general population?

PUS3 p.Ser315= (c.945T>C) is ultra-rare (popmax 0.0358%, eas) (gnomAD).

PUS3 p.Ser315=

c.945T>C · rs751006630 · VCV2521731

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0358%, eas)

Conditions

Inborn genetic diseases

⚠ 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 1.8	GERP -1.7, phastCons 1
Overall
CADD	9.132	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0358% East Asian · 16/44,682 alleles

Filtering AF 0.0224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0182%

Overall 0.00113% 18/1,589,764 alleles · ultra-rare exomes 15/1,437,526 · genomes 3/152,238 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0358%	2,793
Remaining individualsnot grpmax-eligible	0.00163%	61,360
Finnishnot grpmax-eligible	0.0016%	62,636

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.Ser315=
Coding: c.945T>C
MANE Select: NM_031307
dbSNP: rs751006630
Type: single nucleotide variant
Location: chr11:125894286 (GRCh38)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-ser315 (accessed [today's date]).

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