Is SUN5 p.Ser288Asn (c.863G>A) pathogenic?

SUN5 p.Ser288Asn (c.863G>A) is classified Uncertain significance in SUN5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-27). AlphaMissense: likely benign (0.0889); Very rare (popmax 0.0011%, sas).

How common is SUN5 p.Ser288Asn (c.863G>A) in the general population?

SUN5 p.Ser288Asn (c.863G>A) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about SUN5 p.Ser288Asn (c.863G>A)?

AlphaMissense predicts likely benign (score 0.0889) — an in-silico prediction, not a clinical call.

SUN5 p.Ser288Asn

c.863G>A · VCV4177795

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0889 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0889	likely benign
REVEL	0.142	moderately benign-leaning
SaProt	LLR -6.56	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1	GERP 1.6, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 21 kb · p 0.021 · regional, not allelic
Overall
CADD	14.13	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 0.0011% South Asian · 1/91,082 alleles

Overall 0.000186% 3/1,614,104 alleles · very rare exomes 3/1,461,802 · genomes 0/152,302 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,598
South Asiangrpmax	0.0011%	91,082
European (non-Finnish)	8.47e-05%	1,179,972

Ashkenazi Jewish 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: SUN5
Protein: p.Ser288Asn
Coding: c.863G>A
MANE Select: NM_080675
Type: single nucleotide variant
Location: chr20:32985770 (GRCh38)
Gene constraint: LOEUF 1.146 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.31
Residue 288: 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); the sun domain

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-ser288asn (accessed [today's date]).

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