Is SDHD p.Pro24Ser (c.70C>T) pathogenic?

SDHD p.Pro24Ser (c.70C>T) is classified Conflicting classifications of pathogenicity in SDHD (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-06-17). AlphaMissense: likely benign (0.0689); Absent from gnomAD v4.1; Associated with Carney-Stratakis syndrome.

What condition is associated with SDHD p.Pro24Ser (c.70C>T)?

SDHD p.Pro24Ser (c.70C>T) is associated with Carney-Stratakis syndrome, pheochromocytoma, Cowden syndrome 3 (ClinVar).

How common is SDHD p.Pro24Ser (c.70C>T) in the general population?

SDHD p.Pro24Ser (c.70C>T) is absent from gnomAD v4.1 (gnomAD).

How is Carney-Stratakis syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about SDHD p.Pro24Ser (c.70C>T)?

AlphaMissense predicts likely benign (score 0.0689) — an in-silico prediction, not a clinical call.

SDHD p.Pro24Ser

c.70C>T · rs775986509 · VCV1473419

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0689 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Carney-Stratakis syndrome

Computational evidence

Protein change
AlphaMissense	0.0689	likely benign
REVEL	0.59	indeterminate
SaProt	LLR -6.88	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.17	GERP -3.9
Regional constraint	o/e 0.83	unconstrained · MANE · 8,059 bp · p 0.019 · regional, not allelic
Overall
CADD	3.894	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: SDHD
Protein: p.Pro24Ser
Coding: c.70C>T
MANE Select: NM_003002
dbSNP: rs775986509
Type: single nucleotide variant
Location: chr11:112087874 (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

Carney-Stratakis syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pheochromocytoma Cowden syndrome 3 hereditary neoplastic syndrome hereditary pheochromocytoma-paraganglioma

For Carney-Stratakis syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult

Similar variants

SDHD p.Pro24Leu Uncertain significance ★★ ⚠ same residue
SDHD p.Pro24= Likely benign ★★ same residue
SDHD p.Pro24Ala Uncertain significance ★ ⚠ same residue
SDHD p.Pro24fs Pathogenic ★ 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

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-pro24ser (accessed [today's date]).

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