Is SDHD p.Ser68= (c.204C>T) pathogenic?

SDHD p.Ser68= (c.204C>T) is classified Benign/Likely benign in SDHD (ClinVar, Multiple submitters, 23 submitters; last evaluated 2026-02-04). Common (popmax 35.3%, afr) — too common for a highly-penetrant pathogenic allele; Associated with pheochromocytoma/paraganglioma syndrome 1.

What condition is associated with SDHD p.Ser68= (c.204C>T)?

SDHD p.Ser68= (c.204C>T) is associated with pheochromocytoma/paraganglioma syndrome 1, pheochromocytoma, pheochromocytoma/paraganglioma syndrome 3 (ClinVar).

SDHD p.Ser68=

Q: How common is SDHD p.Ser68= (c.204C>T) in the general population?

SDHD p.Ser68= (c.204C>T) is common (popmax 35.3%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.204C>T · rs9919552 · VCV44650

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 23 submitters

gnomAD v4.1

Common

common (popmax 35.3%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

pheochromocytoma/paraganglioma syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.61	GERP -4.3, phastCons 0.056
Overall
CADD	9.481	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 35.3% African / African-American · 26,453/74,864 alleles

Filtering AF 35% ClinGen BA1/BS1 input FAF95, joint · FAF99 34.8%

Overall 2.76% 44,520/1,612,482 alleles · common exomes 28,359/1,460,310 · genomes 16,161/152,172 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	35.3%	3
Middle Eastern	4.63%	22
Remaining individualsnot grpmax-eligible	3.55%	28
Admixed American	3.39%	29
Ashkenazi Jewishnot grpmax-eligible	1.49%	67
European (non-Finnish)	1.05%	95
Finnishnot grpmax-eligible	0.458%	219
South Asian	0.399%	251
East Asian	0.136%	736

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: SDHD
Protein: p.Ser68=
Coding: c.204C>T
MANE Select: NM_003002
dbSNP: rs9919552
Type: single nucleotide variant
Location: chr11:112088901 (GRCh38)
Gene constraint: LOEUF 0.581 · pLI 0.91 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 81.50 · 2 PDB
Residue 68: an α-helix

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

Disease context

pheochromocytoma/paraganglioma syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pheochromocytoma pheochromocytoma/paraganglioma syndrome 3 Carney-Stratakis syndrome Cowden syndrome 3 hereditary neoplastic syndrome hereditary pheochromocytoma-paraganglioma mitochondrial complex 2 deficiency, nuclear type 3

Similar variants

SDHD p.Ser68Arg Uncertain significance ★ ⚠ same residue
SDHD p.Ser68Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
SDHD p.Ser68Thr Uncertain significance ★ ⚠ same residue
SDHD p.Ser68fs Pathogenic ★ same residue
SDHD c.170-1G>T Pathogenic ★★ same condition
SDHD c.170-2A>G Pathogenic/Likely pathogenic ★★ same condition
SDHD c.314+1G>A Pathogenic ★★ same condition
SDHD c.314+1G>T 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/sdhd-p-ser68 (accessed [today's date]).

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