Is SDHA p.Arg97= (c.291G>A) pathogenic?

SDHA p.Arg97= (c.291G>A) is classified Likely benign in SDHA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-10-13). Very rare (popmax 0.0011%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with SDHA p.Arg97= (c.291G>A)?

SDHA p.Arg97= (c.291G>A) is associated with hereditary neoplastic syndrome, pheochromocytoma/paraganglioma syndrome 5, mitochondrial complex II deficiency, nuclear type 1 (ClinVar).

How common is SDHA p.Arg97= (c.291G>A) in the general population?

SDHA p.Arg97= (c.291G>A) is very rare (popmax 0.0011%, sas) (gnomAD).

SDHA p.Arg97=

c.291G>A · rs2477287124 · VCV1797692

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

hereditary neoplastic syndrome

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 0.56	GERP -0.46, phastCons 0.99
Overall
CADD	8.471	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,012 alleles

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

Overall 0.000186% 3/1,612,804 alleles · very rare exomes 3/1,460,516 · genomes 0/152,288 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,012
European (non-Finnish)	0.00017%	589,929

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: SDHA
Protein: p.Arg97=
Coding: c.291G>A
MANE Select: NM_004168
dbSNP: rs2477287124
Type: single nucleotide variant
Location: chr5:224500 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.06 · 5 PDB
Residue 97: an α-helix

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

Disease context

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

Also linked: pheochromocytoma/paraganglioma syndrome 5 mitochondrial complex II deficiency, nuclear type 1

Similar variants

SDHA p.Arg97Thr Uncertain significance ★★ ⚠ same residue
SDHA p.Arg97Ser 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-arg97 (accessed [today's date]).

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