Is SGCD p.Cys221Ser (c.661T>A) pathogenic?

SGCD p.Cys221Ser (c.661T>A) is classified Uncertain significance in SGCD (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). AlphaMissense: ambiguous (0.3672); Absent from gnomAD v4.1; Associated with qualitative or quantitative defects of delta-sarcoglycan.

What condition is associated with SGCD p.Cys221Ser (c.661T>A)?

SGCD p.Cys221Ser (c.661T>A) is associated with qualitative or quantitative defects of delta-sarcoglycan (ClinVar).

How common is SGCD p.Cys221Ser (c.661T>A) in the general population?

SGCD p.Cys221Ser (c.661T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SGCD p.Cys221Ser (c.661T>A)?

AlphaMissense predicts ambiguous (score 0.3672) — an in-silico prediction, not a clinical call.

SGCD p.Cys221Ser

c.661T>A · rs1561899947 · VCV907808

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3672 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

qualitative or quantitative defects of delta-sarcoglycan

Computational evidence

Protein change
AlphaMissense	0.3672	ambiguous
REVEL	0.804	moderately pathogenic-leaning
SaProt	LLR -9.29	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.8, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 430 kb · p 0.031 · regional, not allelic
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM C220S vs ClinVar C221S) — verify the residue.

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: SGCD
Protein: p.Cys221Ser
Coding: c.661T>A
MANE Select: NM_000337
dbSNP: rs1561899947
Type: single nucleotide variant
Location: chr5:156757666 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 81.43

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

Disease context

qualitative or quantitative defects of delta-sarcoglycan — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SGCD p.Cys221Ter Uncertain significance ★ same residue
SGCD p.Cys221Tyr Uncertain significance ★ ⚠ same residue
SGCD c.*1047C>T Uncertain significance ★★ same condition
SGCD c.*158G>A Uncertain significance ★★ same condition
SGCD c.*1719G>A Uncertain significance ★★ same condition
SGCD c.*1856A>T Uncertain significance ★★ same condition
SGCD c.*1906C>G Uncertain significance ★★ same condition
SGCD c.*1907G>A Uncertain significance ★★ same condition

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/sgcd-p-cys221ser (accessed [today's date]).

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