Is SYNRG p.Ile1213= (c.3639C>T) pathogenic?

SYNRG p.Ile1213= (c.3639C>T) is classified Likely benign in SYNRG (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-28). Ultra-rare (popmax 0.0164%, mid); Associated with SYNRG-related disorder.

What condition is associated with SYNRG p.Ile1213= (c.3639C>T)?

SYNRG p.Ile1213= (c.3639C>T) is associated with SYNRG-related disorder (ClinVar).

How common is SYNRG p.Ile1213= (c.3639C>T) in the general population?

SYNRG p.Ile1213= (c.3639C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

SYNRG p.Ile1213=

c.3639C>T · rs754846886 · VCV3045173

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

SYNRG-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.8	GERP -4.4
Overall
CADD	3.788	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.000688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.00136% 22/1,613,838 alleles · ultra-rare exomes 21/1,461,628 · genomes 1/152,210 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,869
African / African-American	0.00267%	37,467
East Asian	0.00223%	44,902
Admixed American	0.00167%	59,992
European (non-Finnish)	0.00119%	84,284

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.Ile1213=
Coding: c.3639C>T
MANE Select: NM_007247
dbSNP: rs754846886
Type: single nucleotide variant
Location: chr17:37536006 (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 p.Gly49Arg Uncertain significance ⚠ same condition
SYNRG c.3518-6C>T Likely benign same condition
SYNRG p.Asp182Asn 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-ile1213 (accessed [today's date]).

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