Is SDHB p.Pro70Ala (c.208C>G) pathogenic?

SDHB p.Pro70Ala (c.208C>G) is classified Uncertain significance in SDHB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-17). AlphaMissense: likely benign (0.2654); Absent from gnomAD v4.1; Associated with pheochromocytoma.

What condition is associated with SDHB p.Pro70Ala (c.208C>G)?

SDHB p.Pro70Ala (c.208C>G) is associated with pheochromocytoma, pheochromocytoma/paraganglioma syndrome 4, gastrointestinal stromal tumor (ClinVar).

How common is SDHB p.Pro70Ala (c.208C>G) in the general population?

SDHB p.Pro70Ala (c.208C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SDHB p.Pro70Ala (c.208C>G)?

AlphaMissense predicts likely benign (score 0.2654) — an in-silico prediction, not a clinical call.

SDHB p.Pro70Ala

c.208C>G · rs200890320 · VCV1387551

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2654 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

pheochromocytoma

Computational evidence

Protein change
AlphaMissense	0.2654	likely benign
REVEL	0.582	indeterminate
SaProt	LLR -12.70	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 35 kb · p 0.67 · regional, not allelic
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SDHB
Protein: p.Pro70Ala
Coding: c.208C>G
MANE Select: NM_003000
dbSNP: rs200890320
Type: single nucleotide variant
Location: chr1:17033138 (GRCh38)
Gene constraint: LOEUF 0.741 · pLI 0.03 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 92.14 · 6 PDB
Residue 70: the 2fe-2s ferredoxin-type domain

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

Similar variants

SDHB p.Pro70Ser Uncertain significance ★★ same residue
SDHB p.Pro70Thr 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
SDHB c.201-2A>C Pathogenic ★★ same condition
SDHB c.286+1G>A 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-pro70ala (accessed [today's date]).

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