Is SDHB p.Tyr61= (c.183T>C) pathogenic?

SDHB p.Tyr61= (c.183T>C) is classified Benign/Likely benign in SDHB (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-11-09). Ultra-rare (popmax 0.0461%, sas); Associated with pheochromocytoma/paraganglioma syndrome 4.

What condition is associated with SDHB p.Tyr61= (c.183T>C)?

SDHB p.Tyr61= (c.183T>C) is associated with pheochromocytoma/paraganglioma syndrome 4, pheochromocytoma, gastrointestinal stromal tumor (ClinVar).

How common is SDHB p.Tyr61= (c.183T>C) in the general population?

SDHB p.Tyr61= (c.183T>C) is ultra-rare (popmax 0.0461%, sas) (gnomAD).

SDHB p.Tyr61=

c.183T>C · rs760169139 · VCV1138286

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0461%, sas)

Conditions

pheochromocytoma/paraganglioma syndrome 4

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 -12	GERP -3.8
Overall
CADD	0.009	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0461% South Asian · 42/91,090 alleles

Filtering AF 0.035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0311%

Overall 0.00291% 47/1,614,068 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0461%	2,169
European (non-Finnish)	0.000424%	236,005

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.Tyr61=
Coding: c.183T>C
MANE Select: NM_003000
dbSNP: rs760169139
Type: single nucleotide variant
Location: chr1:17044778 (GRCh38)
Gene constraint: LOEUF 0.741 · pLI 0.03 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 92.14 · 6 PDB
Residue 61: the 2fe-2s ferredoxin-type domain; a β-strand

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

Disease context

pheochromocytoma/paraganglioma syndrome 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pheochromocytoma gastrointestinal stromal tumor hereditary neoplastic syndrome hereditary pheochromocytoma-paraganglioma

Similar variants

SDHB p.Tyr61Cys Uncertain significance ★★ ⚠ same residue
SDHB p.Tyr61Ter Pathogenic ★ same residue
SDHB p.Tyr61Phe Uncertain significance ★ ⚠ same residue
SDHB p.Tyr61Ser 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-tyr61 (accessed [today's date]).

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