Is SGCD p.Pro88Ser (c.262C>T) pathogenic?

SGCD p.Pro88Ser (c.262C>T) is classified Uncertain significance in SGCD (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-26). AlphaMissense: ambiguous (0.4097); Very rare (popmax 8.5e-05%, nfe); Associated with autosomal recessive limb-girdle muscular dystrophy type 2F.

What condition is associated with SGCD p.Pro88Ser (c.262C>T)?

SGCD p.Pro88Ser (c.262C>T) is associated with autosomal recessive limb-girdle muscular dystrophy type 2F (ClinVar).

How common is SGCD p.Pro88Ser (c.262C>T) in the general population?

SGCD p.Pro88Ser (c.262C>T) is very rare (popmax 8.5e-05%, nfe) (gnomAD).

What do computational predictors say about SGCD p.Pro88Ser (c.262C>T)?

AlphaMissense predicts ambiguous (score 0.4097) — an in-silico prediction, not a clinical call.

SGCD p.Pro88Ser

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.262C>T · rs1489575164 · VCV1004253

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4097 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.5e-05%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2F

Computational evidence

Protein change
AlphaMissense	0.4097	ambiguous
REVEL	0.738	pathogenic-leaning
SaProt	LLR -7.44	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.9, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 430 kb · p 0.031 · regional, not allelic
Overall
CADD	26.4	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 P87S vs ClinVar P88S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.5e-05% European (non-Finnish) · 1/1,176,622 alleles

Overall 6.22e-05% 1/1,608,294 alleles · very rare exomes 1/1,456,012 · genomes 0/152,282 · 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.Pro88Ser
Coding: c.262C>T
MANE Select: NM_000337
dbSNP: rs1489575164
Type: single nucleotide variant
Location: chr5:156508670 (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.Pro88= Likely benign ★ 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-pro88ser (accessed [today's date]).

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