Is SGCA p.Pro216= (c.648C>T) pathogenic?

SGCA p.Pro216= (c.648C>T) is classified Conflicting classifications of pathogenicity in SGCA (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-10-14). Ultra-rare (popmax 0.0164%, mid); Associated with sarcoglycanopathy.

What condition is associated with SGCA p.Pro216= (c.648C>T)?

SGCA p.Pro216= (c.648C>T) is associated with sarcoglycanopathy, autosomal recessive limb-girdle muscular dystrophy type 2D (ClinVar).

How common is SGCA p.Pro216= (c.648C>T) in the general population?

SGCA p.Pro216= (c.648C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

SGCA p.Pro216=

c.648C>T · rs758813493 · VCV324043

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

sarcoglycanopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.23	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -20	GERP -3
Overall
CADD	1.612	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.00986% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0092%

Overall 0.00942% 152/1,613,822 alleles · ultra-rare exomes 145/1,461,694 · genomes 7/152,128 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
Remaining individualsnot grpmax-eligible	0.0144%	6,942
European (non-Finnish)	0.0114%	8,740
Admixed American	0.00333%	30,002
African / African-American	0.00267%	37,449
East Asian	0.00223%	44,876
Finnishnot grpmax-eligible	0.00156%	63,954
South Asian	0.0011%	91,086

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: SGCA
Protein: p.Pro216=
Coding: c.648C>T
MANE Select: NM_000023
dbSNP: rs758813493
Type: single nucleotide variant
Location: chr17:50169155 (GRCh38)
Gene constraint: LOEUF 1.273 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.15

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

Disease context

sarcoglycanopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive limb-girdle muscular dystrophy type 2D

Similar variants

SGCA p.Pro216Ser Uncertain significance ★ ⚠ same residue
SGCA c.37+6T>C Pathogenic ★★★ same condition
SGCA c.585-1G>A Pathogenic ★★★ same condition
SGCA c.957-11C>G Likely pathogenic ★★★ same condition
SGCA p.Ala107Val Likely pathogenic ★★★ ⚠ same condition
SGCA p.Arg192Ter Pathogenic ★★★ same condition
SGCA p.Arg221Cys Likely pathogenic ★★★ same condition
SGCA p.Arg221Pro Likely pathogenic ★★★ 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/sgca-p-pro216 (accessed [today's date]).

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