Is SGCD p.Pro181= (c.543T>G) pathogenic?

SGCD p.Pro181= (c.543T>G) is classified Conflicting classifications of pathogenicity in SGCD (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-28). Rare (popmax 0.129%, afr); Associated with Inborn genetic diseases.

What condition is associated with SGCD p.Pro181= (c.543T>G)?

SGCD p.Pro181= (c.543T>G) is associated with Inborn genetic diseases, autosomal recessive limb-girdle muscular dystrophy type 2F (ClinVar).

How common is SGCD p.Pro181= (c.543T>G) in the general population?

SGCD p.Pro181= (c.543T>G) is rare (popmax 0.129%, afr) (gnomAD).

SGCD p.Pro181=

c.543T>G · rs200451694 · VCV286184

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.129%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.64	GERP 0.26, phastCons 1
Overall
CADD	11.23	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.129% African / African-American · 96/74,640 alleles

Filtering AF 0.108% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.1%

Overall 0.00643% 102/1,586,526 alleles · rare exomes 46/1,434,250 · genomes 56/152,276 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.129%	778
Remaining individualsnot grpmax-eligible	0.00975%	10,255

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.Pro181=
Coding: c.543T>G
MANE Select: NM_000337
dbSNP: rs200451694
Type: single nucleotide variant
Location: chr5:156647504 (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

Similar variants

SGCD p.Pro181Leu Uncertain significance ★ ⚠ same residue
SGCD p.Pro181Ser 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-pro181 (accessed [today's date]).

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