Is SGCD p.Leu70Pro (c.209T>C) pathogenic?

SGCD p.Leu70Pro (c.209T>C) is classified Uncertain significance in SGCD (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). AlphaMissense: likely pathogenic (0.9989); Absent from gnomAD v4.1; Associated with qualitative or quantitative defects of delta-sarcoglycan.

What condition is associated with SGCD p.Leu70Pro (c.209T>C)?

SGCD p.Leu70Pro (c.209T>C) is associated with qualitative or quantitative defects of delta-sarcoglycan (ClinVar).

How common is SGCD p.Leu70Pro (c.209T>C) in the general population?

SGCD p.Leu70Pro (c.209T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SGCD p.Leu70Pro (c.209T>C)?

AlphaMissense predicts likely pathogenic (score 0.9989) — an in-silico prediction, not a clinical call.

SGCD p.Leu70Pro

c.209T>C · rs1756805264 · VCV907807

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9989 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

qualitative or quantitative defects of delta-sarcoglycan

Computational evidence

Protein change
AlphaMissense	0.9989	likely pathogenic · top 1% in SGCD
REVEL	0.978	strongly pathogenic-leaning
SaProt	LLR -18.55	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.9, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 430 kb · p 0.031 · regional, not allelic
Overall
CADD	29.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM L69P vs ClinVar L70P) — 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.Leu70Pro
Coding: c.209T>C
MANE Select: NM_000337
dbSNP: rs1756805264
Type: single nucleotide variant
Location: chr5:156508617 (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 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
SGCD c.*1990C>T Uncertain significance ★★ same condition
SGCD c.*2139C>T 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-leu70pro (accessed [today's date]).

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