Is SYNCRIP p.Arg548= (c.1644C>T) pathogenic?

SYNCRIP p.Arg548= (c.1644C>T) is classified Likely benign in SYNCRIP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-14). Ultra-rare (popmax 0.0846%, sas); Associated with SYNCRIP-related disorder.

What condition is associated with SYNCRIP p.Arg548= (c.1644C>T)?

SYNCRIP p.Arg548= (c.1644C>T) is associated with SYNCRIP-related disorder (ClinVar).

How common is SYNCRIP p.Arg548= (c.1644C>T) in the general population?

SYNCRIP p.Arg548= (c.1644C>T) is ultra-rare (popmax 0.0846%, sas) (gnomAD).

SYNCRIP p.Arg548=

c.1644C>T · rs555193893 · VCV3052971

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0846%, sas)

Conditions

SYNCRIP-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 10	GERP 1.3, phastCons 1
Overall
CADD	21.2	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0846% South Asian · 77/91,030 alleles

Filtering AF 0.0693% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0637%

Overall 0.00552% 89/1,613,386 alleles · ultra-rare exomes 80/1,461,292 · genomes 9/152,094 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0846%	1,182
African / African-American	0.00667%	14,994
Remaining individualsnot grpmax-eligible	0.0048%	20,829
European (non-Finnish)	0.000339%	294,902

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.Arg548=
Coding: c.1644C>T
MANE Select: NM_006372
dbSNP: rs555193893
Type: single nucleotide variant
Location: chr6:85614984 (GRCh38)
Gene constraint: LOEUF 0.249 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 70.83 · 4 PDB
Residue 548: the 'interaction with apobec1' region; the '8 x 3 aa repeats of r-g-g' region; the 'disordered' region; the 'interaction with smn' region

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

Disease context

SYNCRIP-related disorder

Similar variants

SYNCRIP p.Arg548Cys Uncertain significance ★ ⚠ same residue
SYNCRIP p.Ala521Thr Uncertain significance ★ ⚠ same condition
SYNCRIP p.Trp622Arg Uncertain significance ★ ⚠ same condition
SYNCRIP p.Val561Gly Uncertain significance ★ ⚠ same condition
SYNCRIP p.Thr101Ile Uncertain significance ⚠ same condition
SYNCRIP p.Tyr523His Uncertain significance ⚠ same condition
SYNCRIP p.Gln592= Likely benign same condition
SYNCRIP p.Gln596= 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/syncrip-p-arg548 (accessed [today's date]).

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