Is SDHB p.Cys191= (c.573C>T) pathogenic?

SDHB p.Cys191= (c.573C>T) is classified Likely benign in SDHB (ClinVar, Single submitter, 1 submitter; last evaluated 2020-12-09). Very rare (popmax 6.84e-05%); Associated with hereditary neoplastic syndrome.

What condition is associated with SDHB p.Cys191= (c.573C>T)?

SDHB p.Cys191= (c.573C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is SDHB p.Cys191= (c.573C>T) in the general population?

SDHB p.Cys191= (c.573C>T) is very rare (popmax 6.84e-05%) (gnomAD).

SDHB p.Cys191=

c.573C>T · rs2101516529 · VCV1749368

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Conditions

hereditary neoplastic syndrome

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 7.6	GERP 2.1, phastCons 1
Overall
CADD	13.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.84e-05%

Overall 6.84e-05% 1/1,461,618 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.Cys191=
Coding: c.573C>T
MANE Select: NM_003000
dbSNP: rs2101516529
Type: single nucleotide variant
Location: chr1:17024042 (GRCh38)
Gene constraint: LOEUF 0.741 · pLI 0.03 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 92.14 · 6 PDB
Residue 191: the 4fe-4s ferredoxin-type domain; the 'interaction with sdhaf1' region

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SDHB p.Cys191Tyr Pathogenic/Likely pathogenic ★★ same residue
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
SDHB c.201-2A>C Pathogenic ★★ same condition
SDHB c.286+1G>A Pathogenic ★★ same condition
SDHB c.286+2T>A Pathogenic ★★ same condition
SDHB c.286+2T>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-cys191 (accessed [today's date]).

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