Is SDHA p.Val637= (c.1911C>T) pathogenic?

SDHA p.Val637= (c.1911C>T) is classified Benign/Likely benign in SDHA (ClinVar, Multiple submitters, 16 submitters; last evaluated 2026-02-04). Low-frequency (popmax 3.87%, eas); Associated with mitochondrial complex II deficiency, nuclear type 1.

What condition is associated with SDHA p.Val637= (c.1911C>T)?

SDHA p.Val637= (c.1911C>T) is associated with mitochondrial complex II deficiency, nuclear type 1, Leigh syndrome, dilated cardiomyopathy 1GG (ClinVar).

How common is SDHA p.Val637= (c.1911C>T) in the general population?

SDHA p.Val637= (c.1911C>T) is low-frequency (popmax 3.87%, eas) (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.Val637=

c.1911C>T · rs11557098 · VCV224955

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 16 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.87%, eas)

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.
REVEL	0.135	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.1	GERP 0.7, phastCons 0.25
Overall
CADD	9.868	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.87% East Asian · 1,735/44,856 alleles

Filtering AF 3.72% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.66%

Overall 0.159% 2,571/1,612,834 alleles · low-frequency exomes 2,210/1,460,496 · genomes 361/152,338 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	3.87%	26
Remaining individualsnot grpmax-eligible	0.341%	293
South Asian	0.257%	389
Ashkenazi Jewishnot grpmax-eligible	0.24%	417
African / African-American	0.0614%	1,630
Middle Eastern	0.0495%	2,019
Admixed American	0.0383%	2,609
Finnishnot grpmax-eligible	0.0265%	3,767
European (non-Finnish)	0.0194%	5,148

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.Val637=
Coding: c.1911C>T
MANE Select: NM_004168
dbSNP: rs11557098
Type: single nucleotide variant
Location: chr5:256336 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.06 · 5 PDB
Residue 637: 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: Leigh syndrome dilated cardiomyopathy 1GG pheochromocytoma/paraganglioma syndrome 5 hereditary neoplastic syndrome hereditary pheochromocytoma-paraganglioma neurodegeneration with ataxia and late-onset optic atrophy

For Isolated succinate-CoQ reductase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

SDHA p.Val637Ala Uncertain significance ★★ ⚠ same residue
SDHA p.Val637Ile 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-val637 (accessed [today's date]).

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