Is SYNRG p.Pro962= (c.2886A>C) pathogenic?

SYNRG p.Pro962= (c.2886A>C) is classified Benign in SYNRG (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-06). Common (popmax 18.3%, afr) — too common for a highly-penetrant pathogenic allele; Associated with SYNRG-related disorder.

What condition is associated with SYNRG p.Pro962= (c.2886A>C)?

SYNRG p.Pro962= (c.2886A>C) is associated with SYNRG-related disorder (ClinVar).

SYNRG p.Pro962=

Q: How common is SYNRG p.Pro962= (c.2886A>C) in the general population?

SYNRG p.Pro962= (c.2886A>C) is common (popmax 18.3%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2886A>C · rs61753647 · VCV3041461

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 18.3%, afr) — too common for a highly-penetrant pathogenic allele

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 0.11	GERP -1.8, phastCons 0.99
Overall
CADD	6.814	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 18.3% African / African-American · 13,705/74,996 alleles

Filtering AF 18% ClinGen BA1/BS1 input FAF95, joint · FAF99 17.9%

Overall 0.974% 15,726/1,614,174 alleles · common exomes 7,945/1,461,892 · genomes 7,781/152,282 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	18.3%	5
Remaining individualsnot grpmax-eligible	1.25%	80
Admixed American	1.15%	87
Middle Eastern	0.742%	135
South Asian	0.045%	2,222
European (non-Finnish)	0.0386%	2,594
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
Finnishnot grpmax-eligible	0.00312%	32,024

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.Pro962=
Coding: c.2886A>C
MANE Select: NM_007247
dbSNP: rs61753647
Type: single nucleotide variant
Location: chr17:37542288 (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.Ile1213= 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-pro962 (accessed [today's date]).

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