Is SGCD p.Ala134= (c.402T>C) pathogenic?

SGCD p.Ala134= (c.402T>C) is classified Conflicting classifications of pathogenicity in SGCD (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-01-17). Rare (popmax 0.154%, eas); Associated with Inborn genetic diseases.

What condition is associated with SGCD p.Ala134= (c.402T>C)?

SGCD p.Ala134= (c.402T>C) is associated with Inborn genetic diseases, cardiomyopathy, autosomal recessive limb-girdle muscular dystrophy type 2F (ClinVar).

How common is SGCD p.Ala134= (c.402T>C) in the general population?

SGCD p.Ala134= (c.402T>C) is rare (popmax 0.154%, eas) (gnomAD).

SGCD p.Ala134=

c.402T>C · rs190935424 · VCV202084

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

rare (popmax 0.154%, eas)

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 0.1	GERP -2.3, phastCons 0.96
Overall
CADD	4.702	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.154% East Asian · 69/44,832 alleles

Filtering AF 0.125% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.114%

Overall 0.00677% 109/1,609,710 alleles · rare exomes 92/1,457,496 · genomes 17/152,214 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.154%	650
Remaining individualsnot grpmax-eligible	0.0353%	2,833
South Asian	0.011%	9,054
Admixed American	0.00335%	29,841
African / African-American	0.00267%	37,472
European (non-Finnish)	0.00034%	294,280

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.Ala134=
Coding: c.402T>C
MANE Select: NM_000337
dbSNP: rs190935424
Type: single nucleotide variant
Location: chr5:156594951 (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: cardiomyopathy autosomal recessive limb-girdle muscular dystrophy type 2F

Similar variants

SGCD p.Ala134Val 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-ala134 (accessed [today's date]).

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