Is SDHD p.Cys88= (c.264C>T) pathogenic?

SDHD p.Cys88= (c.264C>T) is classified Benign/Likely benign in SDHD (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-04-13). Very rare (popmax 0.000339%, nfe); Associated with pheochromocytoma.

What condition is associated with SDHD p.Cys88= (c.264C>T)?

SDHD p.Cys88= (c.264C>T) is associated with pheochromocytoma, pheochromocytoma/paraganglioma syndrome 1, Carney-Stratakis syndrome (ClinVar).

How common is SDHD p.Cys88= (c.264C>T) in the general population?

SDHD p.Cys88= (c.264C>T) is very rare (popmax 0.000339%, nfe) (gnomAD).

SDHD p.Cys88=

c.264C>T · rs761615413 · VCV1091749

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Conditions

pheochromocytoma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.26	GERP 0.053, phastCons 0.98
Overall
CADD	9.367	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,180,028 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,614,022 alleles · very rare exomes 3/1,461,814 · genomes 1/152,208 · 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: SDHD
Protein: p.Cys88=
Coding: c.264C>T
MANE Select: NM_003002
dbSNP: rs761615413
Type: single nucleotide variant
Location: chr11:112088961 (GRCh38)
Gene constraint: LOEUF 0.581 · pLI 0.91 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 81.50 · 2 PDB

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

Disease context

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

Also linked: pheochromocytoma/paraganglioma syndrome 1 Carney-Stratakis syndrome Cowden syndrome 3 hereditary neoplastic syndrome

Similar variants

SDHD p.Cys88Phe Uncertain significance ★★ ⚠ same residue
SDHD p.Cys88Ter Pathogenic ★ same residue
SDHD p.Cys88Trp Uncertain significance ★ ⚠ 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
SDHD c.315-1G>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/sdhd-p-cys88 (accessed [today's date]).

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