Is SUN5 p.Arg356= (c.1068C>T) pathogenic?

SUN5 p.Arg356= (c.1068C>T) is classified Likely benign in SUN5 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-01). Ultra-rare (popmax 0.0159%, eas); Associated with SUN5-related disorder.

What condition is associated with SUN5 p.Arg356= (c.1068C>T)?

SUN5 p.Arg356= (c.1068C>T) is associated with SUN5-related disorder (ClinVar).

How common is SUN5 p.Arg356= (c.1068C>T) in the general population?

SUN5 p.Arg356= (c.1068C>T) is ultra-rare (popmax 0.0159%, eas) (gnomAD).

SUN5 p.Arg356=

c.1068C>T · rs572445773 · VCV3034980

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0159%, eas)

Conditions

SUN5-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 -7.1	GERP -5.2
Overall
CADD	0.67	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0159% East Asian · 7/43,936 alleles

Filtering AF 0.0074% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00523%

Overall 0.00244% 39/1,599,934 alleles · ultra-rare exomes 31/1,447,618 · genomes 8/152,316 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0159%	6,277
South Asian	0.00571%	17,502
European (non-Finnish)	0.00222%	45,118
Admixed American	0.00172%	58,272

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: SUN5
Protein: p.Arg356=
Coding: c.1068C>T
MANE Select: NM_080675
dbSNP: rs572445773
Type: single nucleotide variant
Location: chr20:32983866 (GRCh38)
Gene constraint: LOEUF 1.146 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.31
Residue 356: a UniProt-annotated variant site (in spgf16; in mouse model abolishes interaction with dnajb13); a UniProt-annotated variant site (in spgf16; significant reduction in protein expression; impaired localization to nuclear inner membrane; in mouse model decreases interaction with dnajb13); a UniProt-annotated variant site (in spgf16; uncertain significance; in mouse model impairs nuclear inner membrane location and decreases interaction with dnajb13); the sun domain

Full SUN5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

SUN5-related disorder

Similar variants

SUN5 p.Arg356Cys Likely pathogenic ★★ same residue
SUN5 c.212-10T>C Likely benign same condition
SUN5 p.Arg149Ter Likely pathogenic ★ same type
SUN5 c.984+8C>T Uncertain significance ★ same type
SUN5 p.Ala206= Uncertain significance ★ same type
SUN5 p.Ala28Ser Uncertain significance ★ ⚠ same type
SUN5 p.Ala364Ser Uncertain significance ★ ⚠ same type
SUN5 p.Ala59Thr 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/sun5-p-arg356 (accessed [today's date]).

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