Is SDHB p.Lys78= (c.234G>A) pathogenic?

SDHB p.Lys78= (c.234G>A) is classified Likely benign in SDHB (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-02). Very rare (popmax 0.000254%, nfe); Associated with pheochromocytoma.

What condition is associated with SDHB p.Lys78= (c.234G>A)?

SDHB p.Lys78= (c.234G>A) is associated with pheochromocytoma, pheochromocytoma/paraganglioma syndrome 4, gastrointestinal stromal tumor (ClinVar).

How common is SDHB p.Lys78= (c.234G>A) in the general population?

SDHB p.Lys78= (c.234G>A) is very rare (popmax 0.000254%, nfe) (gnomAD).

SDHB p.Lys78=

c.234G>A · rs776971836 · VCV1126499

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000254%, 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 0.55	GERP -0.42, phastCons 1
Overall
CADD	8.354	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,802 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,461,626 alleles · very rare

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: SDHB
Protein: p.Lys78=
Coding: c.234G>A
MANE Select: NM_003000
dbSNP: rs776971836
Type: single nucleotide variant
Location: chr1:17033112 (GRCh38)
Gene constraint: LOEUF 0.741 · pLI 0.03 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 92.14 · 6 PDB
Residue 78: the 2fe-2s ferredoxin-type domain; an α-helix

Full SDHB 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 4 gastrointestinal stromal tumor hereditary neoplastic syndrome

Similar variants

SDHB p.Lys78Arg Uncertain significance ★★ ⚠ same residue
SDHB p.Lys78Glu Uncertain significance ★★ ⚠ same residue
SDHB p.Lys78Met Uncertain significance ★★ ⚠ same residue
SDHB p.Lys78Asn Uncertain significance ★ ⚠ same residue
SDHB c.200+1G>A Pathogenic ★★ same condition
SDHB c.200+1G>C Pathogenic/Likely pathogenic ★★ same condition
SDHB c.200+5G>T Likely pathogenic ★★ same condition
SDHB c.201-1G>C 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/sdhb-p-lys78 (accessed [today's date]).

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