Is SGCD p.Phe104Leu (c.310T>C) pathogenic?

SGCD p.Phe104Leu (c.310T>C) is classified Uncertain significance in SGCD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-06). AlphaMissense: ambiguous (0.4331); Very rare (popmax 8.66e-05%, nfe); Associated with autosomal recessive limb-girdle muscular dystrophy type 2F.

What condition is associated with SGCD p.Phe104Leu (c.310T>C)?

SGCD p.Phe104Leu (c.310T>C) is associated with autosomal recessive limb-girdle muscular dystrophy type 2F (ClinVar).

How common is SGCD p.Phe104Leu (c.310T>C) in the general population?

SGCD p.Phe104Leu (c.310T>C) is very rare (popmax 8.66e-05%, nfe) (gnomAD).

What do computational predictors say about SGCD p.Phe104Leu (c.310T>C)?

AlphaMissense predicts ambiguous (score 0.4331) — an in-silico prediction, not a clinical call.

SGCD p.Phe104Leu

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.310T>C · rs989244785 · VCV946096

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4331 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.66e-05%, nfe)

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2F

Computational evidence

Protein change
AlphaMissense	0.4331	ambiguous
REVEL	0.303	indeterminate
SaProt	LLR -2.88	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.2, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 430 kb · p 0.031 · regional, not allelic
Overall
CADD	20.2	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 F103L vs ClinVar F104L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.66e-05% European (non-Finnish) · 1/1,154,320 alleles

Overall 6.37e-05% 1/1,568,630 alleles · very rare exomes 0/1,416,440 · genomes 1/152,190 · joint denominator

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.Phe104Leu
Coding: c.310T>C
MANE Select: NM_000337
dbSNP: rs989244785
Type: single nucleotide variant
Location: chr5:156589246 (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.Arg165Ter Pathogenic ★★★ same condition
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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
SGCD p.Arg33Ter Pathogenic/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-phe104leu (accessed [today's date]).

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