Is SYN1 p.Pro34Arg (c.101C>G) pathogenic?

SYN1 p.Pro34Arg (c.101C>G) is classified Uncertain significance in SYN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-02). AlphaMissense: ambiguous (0.3644); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with SYN1 p.Pro34Arg (c.101C>G)?

SYN1 p.Pro34Arg (c.101C>G) is associated with Inborn genetic diseases (ClinVar).

How common is SYN1 p.Pro34Arg (c.101C>G) in the general population?

SYN1 p.Pro34Arg (c.101C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SYN1 p.Pro34Arg (c.101C>G)?

AlphaMissense predicts ambiguous (score 0.3644) — an in-silico prediction, not a clinical call.

SYN1 p.Pro34Arg

c.101C>G · VCV3964419

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3644 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3644	ambiguous
REVEL	0.085	moderately benign-leaning
SaProt	LLR -9.41	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP -0.72, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 45 kb · p 1.4e-10 · regional, not allelic
Overall
CADD	24.6	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: SYN1
Protein: p.Pro34Arg
Coding: c.101C>G
MANE Select: NM_006950
Type: single nucleotide variant
Location: chrX:47619628 (GRCh38)
Structure: AlphaFold pLDDT 69.86
Residue 34: the 'disordered' region; the 'b; linker' region

Full SYN1 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

SYN1 p.Pro34Leu Uncertain significance ★ ⚠ same residue
SYN1 p.Pro34= Likely benign ★ same residue
SYN1 p.Ala441Asp Uncertain significance ★★ ⚠ same condition
SYN1 p.Arg169Trp Uncertain significance ★★ ⚠ same condition
SYN1 p.Arg424Trp Uncertain significance ★★ ⚠ same condition
SYN1 p.Gly320Ala Uncertain significance ★★ ⚠ same condition
SYN1 p.Gly440Arg Uncertain significance ★★ ⚠ same condition
SYN1 p.Gly47Arg 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/syn1-p-pro34arg (accessed [today's date]).

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