Is SDHA p.Ser628fs (c.1880dup) pathogenic?

SDHA p.Ser628fs (c.1880dup) is classified Uncertain significance in SDHA (ClinVar, Single submitter, 1 submitter; last evaluated 2020-11-16). No gnomAD frequency available for this variant; Associated with pheochromocytoma/paraganglioma syndrome 5.

What condition is associated with SDHA p.Ser628fs (c.1880dup)?

SDHA p.Ser628fs (c.1880dup) is associated with pheochromocytoma/paraganglioma syndrome 5, mitochondrial complex II deficiency, nuclear type 1 (ClinVar).

How common is SDHA p.Ser628fs (c.1880dup) in the general population?

SDHA p.Ser628fs (c.1880dup) is no gnomAD frequency available for this variant (gnomAD).

SDHA p.Ser628fs

c.1880dup · rs1579445237 · VCV646822

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

pheochromocytoma/paraganglioma syndrome 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (14 of 15, 29 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Ser628fs
Coding: c.1880dup
MANE Select: NM_004168
dbSNP: rs1579445237
Type: Duplication
Location: chr5:254477 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.06 · 5 PDB
Residue 628: a β-strand

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.Ser628= Benign/Likely benign ★★ same residue
SDHA p.Ala102fs Pathogenic ★★ same condition
SDHA p.Ala186fs Pathogenic/Likely pathogenic ★★ same condition
SDHA p.Asn416fs Pathogenic ★★ same condition
SDHA p.Cys231fs Pathogenic ★★ same condition
SDHA p.Gly29fs Pathogenic ★★ same condition
SDHA p.Gly316fs Pathogenic/Likely pathogenic ★★ same condition
SDHA p.His34fs 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-ser628fs (accessed [today's date]).

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