Is SGCD p.Leu149= (c.447C>G) pathogenic?

SGCD p.Leu149= (c.447C>G) is classified Likely benign in SGCD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-03-04). Very rare (popmax 0.00134%, afr); Associated with Inborn genetic diseases.

What condition is associated with SGCD p.Leu149= (c.447C>G)?

SGCD p.Leu149= (c.447C>G) is associated with Inborn genetic diseases, autosomal recessive limb-girdle muscular dystrophy type 2F, dilated cardiomyopathy 1L (ClinVar).

How common is SGCD p.Leu149= (c.447C>G) in the general population?

SGCD p.Leu149= (c.447C>G) is very rare (popmax 0.00134%, afr) (gnomAD).

SGCD p.Leu149=

c.447C>G · rs1257378159 · VCV1090822

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00134%, 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 0.89	GERP -0.12, phastCons 1
Overall
CADD	7.506	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,856 alleles

Overall 0.000124% 2/1,612,400 alleles · very rare exomes 1/1,460,306 · genomes 1/152,094 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,856
European (non-Finnish)	8.48e-05%	1,178,946

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.Leu149=
Coding: c.447C>G
MANE Select: NM_000337
dbSNP: rs1257378159
Type: single nucleotide variant
Location: chr5:156594996 (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 dilated cardiomyopathy 1L

Similar variants

SGCD p.Leu149Pro 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
SGCD c.4-1G>T 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-leu149 (accessed [today's date]).

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