Is SDHA p.Ala172= (c.516A>G) pathogenic?

SDHA p.Ala172= (c.516A>G) is classified Benign/Likely benign in SDHA (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-03). Ultra-rare (popmax 0.0217%, amr); Associated with mitochondrial complex II deficiency, nuclear type 1.

What condition is associated with SDHA p.Ala172= (c.516A>G)?

SDHA p.Ala172= (c.516A>G) is associated with mitochondrial complex II deficiency, nuclear type 1, pheochromocytoma/paraganglioma syndrome 5, hereditary neoplastic syndrome (ClinVar).

How common is SDHA p.Ala172= (c.516A>G) in the general population?

SDHA p.Ala172= (c.516A>G) is ultra-rare (popmax 0.0217%, amr) (gnomAD).

How is Isolated succinate-CoQ reductase deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

SDHA p.Ala172=

c.516A>G · rs181278759 · VCV417231

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0217%, amr)

Conditions

mitochondrial complex II deficiency, nuclear type 1

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 -0.88	GERP -3.7
Overall
CADD	5.883	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0217% Admixed American · 13/60,022 alleles

Filtering AF 0.0127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0101%

Overall 0.00198% 32/1,613,932 alleles · ultra-rare exomes 30/1,461,610 · genomes 2/152,322 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0217%	4,617
Remaining individualsnot grpmax-eligible	0.0016%	62,472
European (non-Finnish)	0.00153%	65,557

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.Ala172=
Coding: c.516A>G
MANE Select: NM_004168
dbSNP: rs181278759
Type: single nucleotide variant
Location: chr5:225942 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.06 · 5 PDB
Residue 172: a β-strand

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

Disease context

mitochondrial complex II deficiency, nuclear type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pheochromocytoma/paraganglioma syndrome 5 hereditary neoplastic syndrome

For Isolated succinate-CoQ reductase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

SDHA p.Ala172Glu Uncertain significance ★★ ⚠ same residue
SDHA p.Ala172Thr Uncertain significance ★★ ⚠ same residue
SDHA p.Ala172Val 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

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-ala172 (accessed [today's date]).

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