Is SYNCRIP p.Arg518= (c.1554C>T) pathogenic?

SYNCRIP p.Arg518= (c.1554C>T) is classified Likely benign in SYNCRIP (ClinVar, Single submitter, 2 submitters; last evaluated 2026-05-01). Rare (popmax 0.108%, nfe).

How common is SYNCRIP p.Arg518= (c.1554C>T) in the general population?

SYNCRIP p.Arg518= (c.1554C>T) is rare (popmax 0.108%, nfe) (gnomAD).

SYNCRIP p.Arg518=

c.1554C>T · rs149887697 · VCV2656734

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.108%, nfe)

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 -0.99	GERP -4.5
Overall
CADD	9.383	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.108% European (non-Finnish) · 1,277/1,179,982 alleles

Filtering AF 0.103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.101%

Overall 0.111% 1,796/1,613,446 alleles · rare exomes 1,636/1,461,278 · genomes 160/152,168 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.467%	214
Remaining individualsnot grpmax-eligible	0.115%	868
European (non-Finnish)grpmax	0.108%	924
Admixed American	0.103%	967
South Asian	0.0582%	1,718
African / African-American	0.0416%	2,403
Middle Eastern	0.033%	3,028

Finnish 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: SYNCRIP
Protein: p.Arg518=
Coding: c.1554C>T
MANE Select: NM_006372
dbSNP: rs149887697
Type: single nucleotide variant
Location: chr6:85615074 (GRCh38)
Gene constraint: LOEUF 0.249 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 70.83 · 4 PDB
Residue 518: the 'interaction with apobec1' region; the '8 x 3 aa repeats of r-g-g' region; the 'disordered' region; the 'interaction with smn' region; a modified residue (asymmetric dimethylarginine; by prmt1; alternate); a modified residue (omega-n-methylarginine; by prmt1; alternate)

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

Similar variants

SYNCRIP p.Ala216Thr Uncertain significance ★★ same type
SYNCRIP p.Asn243Ser Uncertain significance ★★ ⚠ same type
SYNCRIP p.Pro440Leu Uncertain significance ★★ ⚠ same type
SYNCRIP p.Pro508Leu Uncertain significance ★★ ⚠ same type
SYNCRIP p.Ser116Gly Uncertain significance ★★ ⚠ same type
SYNCRIP p.Glu612Val Likely benign ★★ ⚠ same type
SYNCRIP p.Arg446Ter Pathogenic ★ same type
SYNCRIP c.803-3C>A 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/syncrip-p-arg518 (accessed [today's date]).

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