Is SDHA p.Lys615= (c.1845G>A) pathogenic?

SDHA p.Lys615= (c.1845G>A) is classified Likely benign in SDHA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-07-01). No allele count reported in gnomAD v4.1 (AN 1,600,004); Associated with pheochromocytoma/paraganglioma syndrome 5.

What condition is associated with SDHA p.Lys615= (c.1845G>A)?

SDHA p.Lys615= (c.1845G>A) is associated with pheochromocytoma/paraganglioma syndrome 5, hereditary neoplastic syndrome, mitochondrial complex II deficiency, nuclear type 1 (ClinVar).

How common is SDHA p.Lys615= (c.1845G>A) in the general population?

SDHA p.Lys615= (c.1845G>A) is no allele count reported in gnomAD v4.1 (AN 1,600,004) (gnomAD).

SDHA p.Lys615=

c.1845G>A · rs1442827207 · VCV1083214

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,600,004)

Conditions

pheochromocytoma/paraganglioma syndrome 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.377	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 0.7, phastCons 1
Overall
CADD	13.66	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,600,004). 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: SDHA
Protein: p.Lys615=
Coding: c.1845G>A
MANE Select: NM_004168
dbSNP: rs1442827207
Type: single nucleotide variant
Location: chr5:254443 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.06 · 5 PDB
Residue 615: an α-helix; a modified residue (n6-succinyllysine)

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

Disease context

pheochromocytoma/paraganglioma syndrome 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome mitochondrial complex II deficiency, nuclear type 1

Similar variants

SDHA p.Lys615Asn Uncertain significance ★ same residue
SDHA p.Lys615Gln Uncertain significance ★ ⚠ same residue
SDHA c.1064+1G>A Likely pathogenic ★★ same condition
SDHA c.1064+1G>T Likely pathogenic ★★ same condition
SDHA c.1064+2T>A Likely pathogenic ★★ same condition
SDHA c.1065-2A>G Likely pathogenic ★★ same condition
SDHA c.1260+1G>T Likely pathogenic ★★ same condition
SDHA c.1260+2T>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/sdha-p-lys615 (accessed [today's date]).

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