Is SDHD p.Ile31= (c.93C>T) pathogenic?

SDHD p.Ile31= (c.93C>T) is classified Benign/Likely benign in SDHD (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-06-01). Ultra-rare (popmax 0.0133%, amr); Associated with pheochromocytoma/paraganglioma syndrome 1.

What condition is associated with SDHD p.Ile31= (c.93C>T)?

SDHD p.Ile31= (c.93C>T) is associated with pheochromocytoma/paraganglioma syndrome 1, pheochromocytoma, Carney-Stratakis syndrome (ClinVar).

How common is SDHD p.Ile31= (c.93C>T) in the general population?

SDHD p.Ile31= (c.93C>T) is ultra-rare (popmax 0.0133%, amr) (gnomAD).

SDHD p.Ile31=

c.93C>T · rs766096986 · VCV779787

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

Conditions

pheochromocytoma/paraganglioma syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.56	GERP -0.56, phastCons 0.99
Overall
CADD	9.056	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0133% Admixed American · 8/60,026 alleles

Filtering AF 0.00661% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00482%

Overall 0.000496% 8/1,613,920 alleles · ultra-rare exomes 8/1,461,600 · genomes 0/152,320 · joint denominator

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: SDHD
Protein: p.Ile31=
Coding: c.93C>T
MANE Select: NM_003002
dbSNP: rs766096986
Type: single nucleotide variant
Location: chr11:112087897 (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

pheochromocytoma/paraganglioma syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

SDHD p.Ile31Met Uncertain significance ★★ ⚠ same residue
SDHD p.Ile31Val Conflicting classifications of pathogenicity ★ ⚠ 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
SDHD c.315-2A>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/sdhd-p-ile31 (accessed [today's date]).

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