Is SYN1 p.Arg6Cys (c.16C>T) pathogenic?

SYN1 p.Arg6Cys (c.16C>T) is classified Uncertain significance in SYN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-07-15). AlphaMissense: likely pathogenic (0.9997); No allele count reported in gnomAD v4.1 (AN 1,169,900).

How common is SYN1 p.Arg6Cys (c.16C>T) in the general population?

SYN1 p.Arg6Cys (c.16C>T) is no allele count reported in gnomAD v4.1 (AN 1,169,900) (gnomAD).

What do computational predictors say about SYN1 p.Arg6Cys (c.16C>T)?

AlphaMissense predicts likely pathogenic (score 0.9997) — an in-silico prediction, not a clinical call.

SYN1 p.Arg6Cys

c.16C>T · rs2147933567 · VCV1313044

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9997 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,169,900)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9997	likely pathogenic · top 2% in SYN1
REVEL	0.572	indeterminate
SaProt	LLR -14.22	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 1.7, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 45 kb · p 1.4e-10 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,169,900). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SYN1
Protein: p.Arg6Cys
Coding: c.16C>T
MANE Select: NM_006950
dbSNP: rs2147933567
Type: single nucleotide variant
Location: chrX:47619713 (GRCh38)
Structure: AlphaFold pLDDT 69.86
Residue 6: the 'disordered' region; the 'a' region

Full SYN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SYN1 p.Arg6= Likely benign ★ same residue
SYN1 c.528-2A>T Pathogenic/Likely pathogenic ★★ same type
SYN1 c.838-2A>G Likely pathogenic ★★ same type
SYN1 p.Arg234Ter Pathogenic ★★ same type
SYN1 p.Arg420Gln Likely pathogenic ★★ ⚠ same type
SYN1 p.Arg422Ter Pathogenic ★★ same type
SYN1 p.Gln249Ter Pathogenic/Likely pathogenic ★★ same type
SYN1 p.Gln483Ter Pathogenic ★★ same type

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-arg6cys (accessed [today's date]).

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