Is SDHD p.Val46= (c.138G>A) pathogenic?

SDHD p.Val46= (c.138G>A) is classified Benign/Likely benign in SDHD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-03-17). No allele count reported in gnomAD v4.1 (AN 1,612,234); Associated with pheochromocytoma/paraganglioma syndrome 1.

What condition is associated with SDHD p.Val46= (c.138G>A)?

SDHD p.Val46= (c.138G>A) is associated with pheochromocytoma/paraganglioma syndrome 1, pheochromocytoma, Carney-Stratakis syndrome (ClinVar).

How common is SDHD p.Val46= (c.138G>A) in the general population?

SDHD p.Val46= (c.138G>A) is no allele count reported in gnomAD v4.1 (AN 1,612,234) (gnomAD).

SDHD p.Val46=

c.138G>A · rs2135267384 · VCV1557992

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,612,234)

Conditions

pheochromocytoma/paraganglioma syndrome 1

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 -0.46	GERP -4.3
Overall
CADD	2.939	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,612,234). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SDHD
Protein: p.Val46=
Coding: c.138G>A
MANE Select: NM_003002
dbSNP: rs2135267384
Type: single nucleotide variant
Location: chr11:112087942 (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

Similar variants

SDHD p.Val46Leu Uncertain significance ★★ ⚠ same residue
SDHD p.Val46Met Uncertain significance ★★ ⚠ same residue
SDHD p.Val46Ala Uncertain significance ★ ⚠ same residue
SDHD p.Val46Glu Uncertain significance ★ ⚠ same residue
SDHD p.Val46fs 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

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-val46 (accessed [today's date]).

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