Is SDHD p.Leu95= (c.283C>T) pathogenic?

SDHD p.Leu95= (c.283C>T) is classified Likely benign in SDHD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-05-19). Absent from gnomAD v4.1; Associated with Carney-Stratakis syndrome.

What condition is associated with SDHD p.Leu95= (c.283C>T)?

SDHD p.Leu95= (c.283C>T) is associated with Carney-Stratakis syndrome, pheochromocytoma, Cowden syndrome 3 (ClinVar).

How common is SDHD p.Leu95= (c.283C>T) in the general population?

SDHD p.Leu95= (c.283C>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.

SDHD p.Leu95=

c.283C>T · rs1865691704 · VCV1155812

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Carney-Stratakis 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 -0.098	GERP -0.58
Overall
CADD	5.841	PHRED · no single calibrated threshold — expert panels disagree

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.Leu95=
Coding: c.283C>T
MANE Select: NM_003002
dbSNP: rs1865691704
Type: single nucleotide variant
Location: chr11:112088980 (GRCh38)
Gene constraint: LOEUF 0.581 · pLI 0.91 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 81.50 · 2 PDB
Residue 95: an α-helix

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

For Carney-Stratakis syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult

Similar variants

SDHD p.Leu95Pro Pathogenic/Likely pathogenic ★★ same residue
SDHD p.Leu95Val Uncertain significance ★ ⚠ same residue
SDHD p.Leu95fs 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
SDHD c.315-1G>A 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/sdhd-p-leu95 (accessed [today's date]).

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