Is SDHC p.Ser83fs (c.248_251del) pathogenic?

SDHC p.Ser83fs (c.248251del) is classified Pathogenic in SDHC (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-09). No gnomAD frequency available for this variant; Associated with hereditary pheochromocytoma-paraganglioma.

What condition is associated with SDHC p.Ser83fs (c.248_251del)?

SDHC p.Ser83fs (c.248_251del) is associated with hereditary pheochromocytoma-paraganglioma, pheochromocytoma/paraganglioma syndrome 3, gastrointestinal stromal tumor (ClinVar).

How common is SDHC p.Ser83fs (c.248_251del) in the general population?

SDHC p.Ser83fs (c.248_251del) is no gnomAD frequency available for this variant (gnomAD).

How is Hereditary pheochromocytoma-paraganglioma inherited?

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

SDHC p.Ser83fs

c.248_251del · rs2102370242 · VCV2637552

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary pheochromocytoma-paraganglioma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 5 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.9	GERP -1.2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SDHC
Protein: p.Ser83fs
Coding: c.248_251del
MANE Select: NM_003001
dbSNP: rs2102370242
Type: Microsatellite
Location: chr1:161356680 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 91.05 · 2 PDB
Residue 83: an α-helix

Full SDHC gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary pheochromocytoma-paraganglioma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pheochromocytoma/paraganglioma syndrome 3 gastrointestinal stromal tumor

For Hereditary pheochromocytoma-paraganglioma (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood
Prevalence: 1-9 / 1 000 000 (Worldwide)

Similar variants

SDHC p.Ser83Cys Uncertain significance ★★ ⚠ same residue
SDHC p.Ser83Ala Uncertain significance ★ ⚠ same residue
SDHC p.Ser83Pro Uncertain significance ★ ⚠ same residue
SDHC p.Ser83= Likely benign ★ same residue
SDHC p.Leu84fs Pathogenic ★★ same condition
SDHC c.241+9_241+10del Likely benign ★★ same condition
SDHC p.Glu37del Uncertain significance ★ same condition
SDHC p.Ser83Thr Uncertain significance ★ ⚠ same residue

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/sdhc-p-ser83fs (accessed [today's date]).

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