Is SYNRG p.Gly13Arg (c.37G>A) pathogenic?

SYNRG p.Gly13Arg (c.37G>A) is classified Uncertain significance in SYNRG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-29). AlphaMissense: likely pathogenic (0.7042); Very rare (popmax 0.00034%).

How common is SYNRG p.Gly13Arg (c.37G>A) in the general population?

SYNRG p.Gly13Arg (c.37G>A) is very rare (popmax 0.00034%) (gnomAD).

What do computational predictors say about SYNRG p.Gly13Arg (c.37G>A)?

AlphaMissense predicts likely pathogenic (score 0.7042) — an in-silico prediction, not a clinical call.

SYNRG p.Gly13Arg

c.37G>A · VCV4591965

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7042 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00034%)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7042	likely pathogenic
REVEL	0.06	moderately benign-leaning
SaProt	LLR -10.59	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.4	GERP 0.78, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 25 kb · p 0.024 · regional, not allelic
Overall
CADD	23.2	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

Grpmax group 0.00034%

Overall 0.00034% 5/1,468,540 alleles · very rare exomes 5/1,316,194 · genomes 0/152,346 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: SYNRG
Protein: p.Gly13Arg
Coding: c.37G>A
MANE Select: NM_007247
Type: single nucleotide variant
Location: chr17:37609319 (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

Similar variants

SYNRG c.372-1G>A Uncertain significance ★ same type
SYNRG c.3813+5G>A Uncertain significance ★ same type
SYNRG p.Ala1246Val Uncertain significance ★ ⚠ same type
SYNRG p.Ala1291Thr Uncertain significance ★ ⚠ same type
SYNRG p.Ala15Thr Uncertain significance ★ ⚠ same type
SYNRG p.Ala171Val Uncertain significance ★ ⚠ same type
SYNRG p.Ala17Val Uncertain significance ★ ⚠ same type
SYNRG p.Ala261Thr Uncertain significance ★ ⚠ 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/synrg-p-gly13arg (accessed [today's date]).

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