Is SGCE p.Cys258Ser (c.772T>A) pathogenic?

SGCE p.Cys258Ser (c.772T>A) is classified Uncertain significance in SGCE (ClinVar, Single submitter, 1 submitter; last evaluated 2020-01-15). AlphaMissense: likely pathogenic (0.9956); Absent from gnomAD v4.1.

How common is SGCE p.Cys258Ser (c.772T>A) in the general population?

SGCE p.Cys258Ser (c.772T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SGCE p.Cys258Ser (c.772T>A)?

AlphaMissense predicts likely pathogenic (score 0.9956) — an in-silico prediction, not a clinical call.

SGCE p.Cys258Ser

c.772T>A · rs1799568147 · VCV1315294

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9956 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.9956	likely pathogenic
REVEL	0.958	strongly pathogenic-leaning
SaProt	LLR -9.52	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 71 kb · p 0.00058 · regional, not allelic
Overall
CADD	27.4	PHRED · no single calibrated threshold — expert panels disagree

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

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: SGCE
Protein: p.Cys258Ser
Coding: c.772T>A
MANE Select: NM_003919
dbSNP: rs1799568147
Type: single nucleotide variant
Location: chr7:94603343 (GRCh38)

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

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/sgce-p-cys258ser (accessed [today's date]).

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