Is SGCD p.Phe38Leu (c.112T>C) pathogenic?

SGCD p.Phe38Leu (c.112T>C) is classified Uncertain significance in SGCD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-08). AlphaMissense: likely pathogenic (0.8902); Very rare (popmax 0.00178%, nfe); Associated with autosomal recessive limb-girdle muscular dystrophy type 2F.

What condition is associated with SGCD p.Phe38Leu (c.112T>C)?

SGCD p.Phe38Leu (c.112T>C) is associated with autosomal recessive limb-girdle muscular dystrophy type 2F (ClinVar).

How common is SGCD p.Phe38Leu (c.112T>C) in the general population?

SGCD p.Phe38Leu (c.112T>C) is very rare (popmax 0.00178%, nfe) (gnomAD).

What do computational predictors say about SGCD p.Phe38Leu (c.112T>C)?

AlphaMissense predicts likely pathogenic (score 0.8902) — an in-silico prediction, not a clinical call.

SGCD p.Phe38Leu

Q: How is Delta-sarcoglycan-related limb-girdle muscular dystrophy R6 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.112T>C · rs750206304 · VCV2178479

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8902 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00178%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2F

Computational evidence

Protein change
AlphaMissense	0.8902	likely pathogenic
REVEL	0.654	pathogenic-leaning
SaProt	LLR -9.33	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.8	GERP 2, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 430 kb · p 0.031 · regional, not allelic
Overall
CADD	23.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM F37L vs ClinVar F38L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00178% European (non-Finnish) · 21/1,179,284 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.00136% 22/1,612,480 alleles · very rare exomes 21/1,460,332 · genomes 1/152,148 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00178%	56,156
Remaining individualsnot grpmax-eligible	0.0016%	62,412

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.Phe38Leu
Coding: c.112T>C
MANE Select: NM_000337
dbSNP: rs750206304
Type: single nucleotide variant
Location: chr5:156344597 (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

autosomal recessive limb-girdle muscular dystrophy type 2F — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Delta-sarcoglycan-related limb-girdle muscular dystrophy R6 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

SGCD p.Phe38= Likely benign ★ same residue
SGCD p.Phe38Cys 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-phe38leu (accessed [today's date]).

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