Is SDHD p.Asp118= (c.354T>C) pathogenic?

SDHD p.Asp118= (c.354T>C) is classified Benign/Likely benign in SDHD (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-03-18). Very rare (popmax 8.48e-05%, nfe); Associated with pheochromocytoma/paraganglioma syndrome 1.

What condition is associated with SDHD p.Asp118= (c.354T>C)?

SDHD p.Asp118= (c.354T>C) is associated with pheochromocytoma/paraganglioma syndrome 1, pheochromocytoma, Carney-Stratakis syndrome (ClinVar).

How common is SDHD p.Asp118= (c.354T>C) in the general population?

SDHD p.Asp118= (c.354T>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

SDHD p.Asp118=

c.354T>C · rs911663426 · VCV1158878

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

pheochromocytoma/paraganglioma syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.149	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -3.2	GERP -4.3
Overall
CADD	4.828	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,868 alleles

Overall 6.2e-05% 1/1,612,080 alleles · very rare exomes 1/1,459,704 · genomes 0/152,376 · 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.Asp118=
Coding: c.354T>C
MANE Select: NM_003002
dbSNP: rs911663426
Type: single nucleotide variant
Location: chr11:112094844 (GRCh38)
Gene constraint: LOEUF 0.581 · pLI 0.91 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 81.50 · 2 PDB
Residue 118: an α-helix

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.Asp118Gly Uncertain significance ★★ ⚠ same residue
SDHD p.Asp118Ala Uncertain significance ★ ⚠ same residue
SDHD p.Asp118Asn Uncertain significance ★ ⚠ same residue
SDHD p.Asp118Glu Conflicting classifications of pathogenicity ★ ⚠ same residue
SDHD p.Asp118fs Pathogenic ★ same residue
SDHD p.Asp118Ile Uncertain significance ★ same residue
SDHD c.170-1G>T Pathogenic ★★ same condition
SDHD c.170-2A>G 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-asp118 (accessed [today's date]).

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