Is SUN1 p.Ala451= (c.1353C>T) pathogenic?

SUN1 p.Ala451= (c.1353C>T) is classified Likely benign in SUN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-01). Absent from gnomAD v4.1.

How common is SUN1 p.Ala451= (c.1353C>T) in the general population?

SUN1 p.Ala451= (c.1353C>T) is absent from gnomAD v4.1 (gnomAD).

SUN1 p.Ala451=

c.1353C>T · VCV4085131

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.032	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.54	GERP 1.7
Overall
CADD	9.326	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SUN1
Protein: p.Ala451=
Coding: c.1353C>T
MANE Select: NM_001130965
Type: single nucleotide variant
Location: chr7:856360 (GRCh38)
Gene constraint: LOEUF 0.712 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.99 · 8 PDB

Full SUN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SUN1 p.Ala179Thr Uncertain significance ★★ same type
SUN1 p.Ala203Thr Uncertain significance ★★ same type
SUN1 p.Ala232Val Uncertain significance ★★ same type
SUN1 p.Ala236Thr Uncertain significance ★★ same type
SUN1 p.Ala255Thr Uncertain significance ★★ same type
SUN1 p.Ala256Val Uncertain significance ★★ same type
SUN1 p.Ala404Thr Uncertain significance ★★ same type
SUN1 p.Ala414Thr 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/sun1-p-ala451 (accessed [today's date]).

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