Is SYNRG p.Gly49Arg (c.145G>A) pathogenic?

SYNRG p.Gly49Arg (c.145G>A) is classified Uncertain significance in SYNRG (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-07-20). AlphaMissense: likely pathogenic (0.8076); Absent from gnomAD v4.1; Associated with SYNRG-related disorder.

What condition is associated with SYNRG p.Gly49Arg (c.145G>A)?

SYNRG p.Gly49Arg (c.145G>A) is associated with SYNRG-related disorder (ClinVar).

How common is SYNRG p.Gly49Arg (c.145G>A) in the general population?

SYNRG p.Gly49Arg (c.145G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SYNRG p.Gly49Arg (c.145G>A)?

AlphaMissense predicts likely pathogenic (score 0.8076) — an in-silico prediction, not a clinical call.

SYNRG p.Gly49Arg

c.145G>A · VCV3346733

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8076 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

SYNRG-related disorder

Computational evidence

Protein change
AlphaMissense	0.8076	likely pathogenic
REVEL	0.364	indeterminate
SaProt	LLR -7.37	tolerated
⇒ AlphaMissense calls this damaging; SaProt 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 0.85	unconstrained · MANE · 25 kb · p 0.024 · regional, not allelic
Overall
CADD	27.6	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: SYNRG
Protein: p.Gly49Arg
Coding: c.145G>A
MANE Select: NM_007247
Type: single nucleotide variant
Location: chr17:37596318 (GRCh38)
Gene constraint: LOEUF 0.38 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 48.74 · 1 PDB

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

Disease context

SYNRG-related disorder

Similar variants

SYNRG c.372-1G>A Uncertain significance ★ same condition
SYNRG p.Phe1094Val Uncertain significance ★ ⚠ same condition
SYNRG p.Asp572Glu Uncertain significance ⚠ same condition
SYNRG p.Glu1080Lys Uncertain significance same condition
SYNRG c.3518-6C>T Likely benign same condition
SYNRG p.Asp182Asn Likely benign ⚠ same condition
SYNRG p.Ile1213= Likely benign same condition
SYNRG p.Lys1104= Likely benign 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/synrg-p-gly49arg (accessed [today's date]).

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