Is SGCD p.Leu41= (c.123C>G) pathogenic?

SGCD p.Leu41= (c.123C>G) is classified Conflicting classifications of pathogenicity in SGCD (ClinVar, Conflicting submitters, 12 submitters; last evaluated 2026-02-03). Rare (popmax 0.196%, afr); Associated with Inborn genetic diseases.

How common is SGCD p.Leu41= (c.123C>G) in the general population?

SGCD p.Leu41= (c.123C>G) is rare (popmax 0.196%, afr) (gnomAD).

SGCD p.Leu41=

Q: What condition is associated with SGCD p.Leu41= (c.123C>G)?

SGCD p.Leu41= (c.123C>G) is associated with Inborn genetic diseases, autosomal recessive limb-girdle muscular dystrophy type 2F, qualitative or quantitative defects of delta-sarcoglycan (ClinVar).

c.123C>G · rs200670993 · VCV48115

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 12 submitters

gnomAD v4.1

Rare

rare (popmax 0.196%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.46	GERP -0.88, phastCons 0.99
Overall
CADD	7.638	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.196% African / African-American · 147/74,892 alleles

Filtering AF 0.17% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.161%

Overall 0.0136% 219/1,612,076 alleles · rare exomes 149/1,459,892 · genomes 70/152,184 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.196%	509
Middle Eastern	0.0825%	1,212
Remaining individualsnot grpmax-eligible	0.0416%	2,401
Admixed American	0.0318%	3,149
South Asian	0.00552%	18,124
European (non-Finnish)	0.00144%	69,353

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: SGCD
Protein: p.Leu41=
Coding: c.123C>G
MANE Select: NM_000337
dbSNP: rs200670993
Type: single nucleotide variant
Location: chr5:156344608 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive limb-girdle muscular dystrophy type 2F qualitative or quantitative defects of delta-sarcoglycan

Similar variants

SGCD p.Leu41Ile Uncertain significance ★ ⚠ same residue
SGCD p.Leu41Pro Uncertain significance ★ ⚠ same residue
SGCD p.Arg165Ter Pathogenic ★★★ same condition
SGCD p.Arg97Ter Pathogenic ★★★ same condition
SGCD p.Arg31Trp Uncertain significance ★★★ ⚠ same condition
SGCD p.Ile64Thr Uncertain significance ★★★ ⚠ same condition
SGCD c.192+1G>A Likely pathogenic ★★ same condition
SGCD c.294+1G>A 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/sgcd-p-leu41 (accessed [today's date]).

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