Is SPRTN p.Pro172Arg (c.515C>G) pathogenic?

SPRTN p.Pro172Arg (c.515C>G) is classified Uncertain significance in SPRTN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-15). AlphaMissense: likely benign (0.2068); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with SPRTN p.Pro172Arg (c.515C>G)?

SPRTN p.Pro172Arg (c.515C>G) is associated with Inborn genetic diseases (ClinVar).

How common is SPRTN p.Pro172Arg (c.515C>G) in the general population?

SPRTN p.Pro172Arg (c.515C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SPRTN p.Pro172Arg (c.515C>G)?

AlphaMissense predicts likely benign (score 0.2068) — an in-silico prediction, not a clinical call.

SPRTN p.Pro172Arg

c.515C>G · VCV4632075

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2068 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2068	likely benign
REVEL	0.503	indeterminate
SaProt	LLR -10.37	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 13 kb · p 8.6e-08 · regional, not allelic
Overall
CADD	25.3	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: SPRTN
Protein: p.Pro172Arg
Coding: c.515C>G
MANE Select: NM_032018
Type: single nucleotide variant
Location: chr1:231351368 (GRCh38)
Gene constraint: LOEUF 0.531 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 66.07 · 3 PDB
Residue 172: the sprt-like domain; an α-helix

Full SPRTN 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

SPRTN p.Ala226Pro Uncertain significance ★ ⚠ same condition
SPRTN p.Ala63Val Uncertain significance ★ ⚠ same condition
SPRTN p.Arg163Gln Uncertain significance ★ ⚠ same condition
SPRTN p.Arg164Gln Uncertain significance ★ ⚠ same condition
SPRTN p.Arg168Cys Uncertain significance ★ same condition
SPRTN p.Arg351Gly Uncertain significance ★ ⚠ same condition
SPRTN p.Arg351Lys Uncertain significance ★ ⚠ same condition
SPRTN p.Arg370Lys 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/sprtn-p-pro172arg (accessed [today's date]).

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