Is SUN1 p.Phe777Ser (c.2330T>C) pathogenic?

SUN1 p.Phe777Ser (c.2330T>C) is classified Uncertain significance in SUN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). Absent from gnomAD v4.1.

How common is SUN1 p.Phe777Ser (c.2330T>C) in the general population?

SUN1 p.Phe777Ser (c.2330T>C) is absent from gnomAD v4.1 (gnomAD).

SUN1 p.Phe777Ser

c.2330T>C · VCV4836423

Uncertain significance Single submitter

Classification

Uncertain significance

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	0.839	moderately pathogenic-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 5.5, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 13 kb · p 0.0008 · regional, not allelic
Overall
CADD	32.0	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.Phe777Ser
Coding: c.2330T>C
MANE Select: NM_001130965
Type: single nucleotide variant
Location: chr7:873303 (GRCh38)
Gene constraint: LOEUF 0.712 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.99 · 8 PDB
Residue 777: the sun domain; a β-strand; the 'sufficient for interaction with syne1 and syne2' region

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

Similar variants

SUN1 p.Phe777Leu Uncertain significance ★ same residue
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

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-phe777ser (accessed [today's date]).

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