Is SDHA p.Ser2Ter (c.5C>A) pathogenic?

SDHA p.Ser2Ter (c.5C>A) is classified Pathogenic in SDHA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-01). No allele count reported in gnomAD v4.1 (AN 1,459,838); Associated with pheochromocytoma/paraganglioma syndrome 5.

What condition is associated with SDHA p.Ser2Ter (c.5C>A)?

SDHA p.Ser2Ter (c.5C>A) is associated with pheochromocytoma/paraganglioma syndrome 5, mitochondrial complex II deficiency, nuclear type 1 (ClinVar).

How common is SDHA p.Ser2Ter (c.5C>A) in the general population?

SDHA p.Ser2Ter (c.5C>A) is no allele count reported in gnomAD v4.1 (AN 1,459,838) (gnomAD).

SDHA p.Ser2Ter

c.5C>A · rs780064103 · VCV644096

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,459,838)

Conditions

pheochromocytoma/paraganglioma syndrome 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 15
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP 0.29, phastCons 1
Overall
CADD	40.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,459,838). 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.Ser2Ter
Coding: c.5C>A
MANE Select: NM_004168
dbSNP: rs780064103
Type: single nucleotide variant
Location: chr5:218360 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.06 · 5 PDB

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: mitochondrial complex II deficiency, nuclear type 1

Similar variants

SDHA p.Ser2Pro Uncertain significance ★★ ⚠ same residue
SDHA p.Ser2= Benign/Likely benign ★★ same residue
SDHA p.Ser2Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
SDHA p.Ser2Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
SDHA p.Ser2Trp 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

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-ser2ter (accessed [today's date]).

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