Is PUS7 p.Pro245Ser (c.733C>T) pathogenic?

PUS7 p.Pro245Ser (c.733C>T) is classified Uncertain significance in PUS7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-17). AlphaMissense: likely pathogenic (0.5756); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PUS7 p.Pro245Ser (c.733C>T)?

PUS7 p.Pro245Ser (c.733C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PUS7 p.Pro245Ser (c.733C>T) in the general population?

PUS7 p.Pro245Ser (c.733C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PUS7 p.Pro245Ser (c.733C>T)?

AlphaMissense predicts likely pathogenic (score 0.5756) — an in-silico prediction, not a clinical call.

PUS7 p.Pro245Ser

c.733C>T · rs2484938901 · VCV2308513

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5756 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5756	likely pathogenic
REVEL	0.191	benign-leaning
SaProt	LLR -4.54	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 7, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 51 kb · p 0.015 · regional, not allelic
Overall
CADD	25.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PUS7
Protein: p.Pro245Ser
Coding: c.733C>T
MANE Select: NM_019042
dbSNP: rs2484938901
Type: single nucleotide variant
Location: chr7:105495251 (GRCh38)
Gene constraint: LOEUF 0.727 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.67 · 1 PDB

Full PUS7 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

Similar variants

PUS7 p.Arg661His Uncertain significance ★★ ⚠ same condition
PUS7 p.Met104Val Uncertain significance ★★ ⚠ same condition
PUS7 p.Glu180Lys Likely benign ★★ same condition
PUS7 c.398+1G>T Conflicting classifications of pathogenicity ★ same condition
PUS7 p.Ala236Thr Uncertain significance ★ ⚠ same condition
PUS7 p.Ala314Ser Uncertain significance ★ ⚠ same condition
PUS7 p.Ala362Thr Uncertain significance ★ ⚠ same condition
PUS7 p.Ala590Val Uncertain significance ★ ⚠ same condition

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/pus7-p-pro245ser (accessed [today's date]).

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