Is SDHD p.Asp146= (c.438T>C) pathogenic?

SDHD p.Asp146= (c.438T>C) is classified Benign/Likely benign in SDHD (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-06-01). Very rare (popmax 0.00891%, eas); Associated with pheochromocytoma.

What condition is associated with SDHD p.Asp146= (c.438T>C)?

SDHD p.Asp146= (c.438T>C) is associated with pheochromocytoma, pheochromocytoma/paraganglioma syndrome 1, Carney-Stratakis syndrome (ClinVar).

How common is SDHD p.Asp146= (c.438T>C) in the general population?

SDHD p.Asp146= (c.438T>C) is very rare (popmax 0.00891%, eas) (gnomAD).

SDHD p.Asp146=

c.438T>C · rs201328474 · VCV480867

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Conditions

pheochromocytoma

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 -8.3	GERP -4.3
Overall
CADD	1.865	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,886 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00149% 24/1,611,358 alleles · very rare exomes 22/1,459,130 · genomes 2/152,228 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,222
South Asian	0.00549%	18,199
African / African-American	0.00267%	37,429
Remaining individualsnot grpmax-eligible	0.00161%	62,286
European (non-Finnish)	0.00102%	98,277

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.Asp146=
Coding: c.438T>C
MANE Select: NM_003002
dbSNP: rs201328474
Type: single nucleotide variant
Location: chr11:112094928 (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 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pheochromocytoma/paraganglioma syndrome 1 Carney-Stratakis syndrome Cowden syndrome 3 hereditary neoplastic syndrome hereditary pheochromocytoma-paraganglioma

Similar variants

SDHD p.Asp146Asn Uncertain significance ★★ ⚠ same residue
SDHD p.Asp146Tyr Uncertain significance ★ ⚠ same residue
SDHD p.Asp146His Uncertain significance ★ ⚠ 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-asp146 (accessed [today's date]).

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