Is SUN5 p.Gln369Pro (c.1106A>C) pathogenic?

SUN5 p.Gln369Pro (c.1106A>C) is classified Uncertain significance in SUN5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-18). AlphaMissense: likely benign (0.0614); Very rare (popmax 0.000345%, nfe).

How common is SUN5 p.Gln369Pro (c.1106A>C) in the general population?

SUN5 p.Gln369Pro (c.1106A>C) is very rare (popmax 0.000345%, nfe) (gnomAD).

What do computational predictors say about SUN5 p.Gln369Pro (c.1106A>C)?

AlphaMissense predicts likely benign (score 0.0614) — an in-silico prediction, not a clinical call.

SUN5 p.Gln369Pro

c.1106A>C · rs928843192 · VCV2327318

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0614 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000345%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0614	likely benign
REVEL	0.021	moderately benign-leaning
SaProt	LLR -5.93	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.67	GERP -1, phastCons 0.14
Regional constraint	o/e 0.90	unconstrained · MANE · 21 kb · p 0.021 · regional, not allelic
Overall
CADD	13.81	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000345% European (non-Finnish) · 4/1,160,622 alleles

Filtering AF 8.1e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000254% 4/1,576,584 alleles · very rare exomes 3/1,424,340 · genomes 1/152,244 · joint denominator

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.Gln369Pro
Coding: c.1106A>C
MANE Select: NM_080675
dbSNP: rs928843192
Type: single nucleotide variant
Location: chr20:32983828 (GRCh38)
Gene constraint: LOEUF 1.146 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.31
Residue 369: 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)

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

Similar variants

SUN5 p.Arg356Cys Likely pathogenic ★★ same type
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
SUN5 p.Ala84Val 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-gln369pro (accessed [today's date]).

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