Is SYNRG p.Asp182Asn (c.544G>A) pathogenic?

SYNRG p.Asp182Asn (c.544G>A) is classified Likely benign in SYNRG (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-21). AlphaMissense: likely pathogenic (0.784); Rare (popmax 0.802%, nfe); Associated with SYNRG-related disorder.

What condition is associated with SYNRG p.Asp182Asn (c.544G>A)?

SYNRG p.Asp182Asn (c.544G>A) is associated with SYNRG-related disorder (ClinVar).

How common is SYNRG p.Asp182Asn (c.544G>A) in the general population?

SYNRG p.Asp182Asn (c.544G>A) is rare (popmax 0.802%, nfe) (gnomAD).

What do computational predictors say about SYNRG p.Asp182Asn (c.544G>A)?

AlphaMissense predicts likely pathogenic (score 0.784) — an in-silico prediction, not a clinical call.

SYNRG p.Asp182Asn

c.544G>A · rs148948026 · VCV3041248

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.784 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.802%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

SYNRG-related disorder

Computational evidence

Protein change
AlphaMissense	0.784	likely pathogenic
REVEL	0.199	benign-leaning
SaProt	LLR -6.35	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.7, phastCons 1
Regional constraint	o/e 0.27	constrained · MANE · 74 bp · p 7.8e-05 · regional, not allelic
Overall
CADD	26.8	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 0.802% European (non-Finnish) · 9,457/1,179,758 alleles

Filtering AF 0.788% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.783%

Overall 0.638% 10,288/1,613,796 alleles · rare exomes 9,595/1,461,504 · genomes 693/152,292 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	3.95%	25
European (non-Finnish)grpmax	0.802%	125
Remaining individualsnot grpmax-eligible	0.491%	204
Ashkenazi Jewishnot grpmax-eligible	0.324%	308
Admixed American	0.257%	390
Finnishnot grpmax-eligible	0.212%	471
African / African-American	0.124%	807
Middle Eastern	0.033%	3,031
South Asian	0.00769%	13,009

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp182Asn
Coding: c.544G>A
MANE Select: NM_007247
dbSNP: rs148948026
Type: single nucleotide variant
Location: chr17:37584693 (GRCh38)
Gene constraint: LOEUF 0.38 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 48.74 · 1 PDB
Residue 182: the 'disordered' region

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.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-asp182asn (accessed [today's date]).

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