Is SDHD p.Ala90= (c.270G>T) pathogenic?

SDHD p.Ala90= (c.270G>T) is classified Likely benign in SDHD (ClinVar, Single submitter, 1 submitter; last evaluated 2021-02-17). Very rare (popmax 0.000169%, nfe); Associated with Cowden syndrome 3.

What condition is associated with SDHD p.Ala90= (c.270G>T)?

SDHD p.Ala90= (c.270G>T) is associated with Cowden syndrome 3, pheochromocytoma, Carney-Stratakis syndrome (ClinVar).

How common is SDHD p.Ala90= (c.270G>T) in the general population?

SDHD p.Ala90= (c.270G>T) is very rare (popmax 0.000169%, nfe) (gnomAD).

SDHD p.Ala90=

c.270G>T · rs766656463 · VCV1534367

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Conditions

Cowden syndrome 3

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 0.36	GERP -3.9
Overall
CADD	7.986	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,018 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,614,122 alleles · very rare exomes 2/1,461,840 · genomes 0/152,282 · 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.Ala90=
Coding: c.270G>T
MANE Select: NM_003002
dbSNP: rs766656463
Type: single nucleotide variant
Location: chr11:112088967 (GRCh38)
Gene constraint: LOEUF 0.581 · pLI 0.91 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 81.50 · 2 PDB
Residue 90: an α-helix

Full SDHD gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cowden syndrome 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pheochromocytoma Carney-Stratakis syndrome

Similar variants

SDHD p.Ala90Gly Uncertain significance ★★ ⚠ same residue
SDHD p.Ala90Glu Conflicting classifications of pathogenicity ★ ⚠ same residue
SDHD p.Ala90Thr Uncertain significance ★ ⚠ same residue
SDHD p.Ala90Val Conflicting classifications of pathogenicity ★ ⚠ same residue
SDHD p.Ala90Leu Uncertain significance ★★ same residue
SDHD p.Ala90Ser 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-ala90 (accessed [today's date]).

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