Is SDHA p.Phe390= (c.1170C>T) pathogenic?

SDHA p.Phe390= (c.1170C>T) is classified Benign in SDHA (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-02-04). Common (popmax 33.1%, afr) — too common for a highly-penetrant pathogenic allele; Associated with neurodegeneration with ataxia and late-onset optic atrophy.

SDHA p.Phe390=

Q: What condition is associated with SDHA p.Phe390= (c.1170C>T)?

SDHA p.Phe390= (c.1170C>T) is associated with neurodegeneration with ataxia and late-onset optic atrophy, Leigh syndrome, dilated cardiomyopathy 1GG (ClinVar).

Q: How common is SDHA p.Phe390= (c.1170C>T) in the general population?

SDHA p.Phe390= (c.1170C>T) is common (popmax 33.1%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1170C>T · rs35277230 · VCV130274

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

gnomAD v4.1

Common

common (popmax 33.1%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

neurodegeneration with ataxia and late-onset optic atrophy

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 -6.8	GERP -3.5
Overall
CADD	7.205	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 33.1% African / African-American · 24,826/74,940 alleles

Filtering AF 32.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 32.6%

Overall 1.95% 31,421/1,613,954 alleles · common exomes 16,827/1,461,752 · genomes 14,594/152,202 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	33.1%	3
Middle Eastern	3.22%	31
Admixed American	2.98%	34
Remaining individualsnot grpmax-eligible	2.74%	37
Ashkenazi Jewishnot grpmax-eligible	1.06%	95
European (non-Finnish)	0.212%	472
South Asian	0.0911%	1,097
Finnishnot grpmax-eligible	0.00781%	12,807

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.Phe390=
Coding: c.1170C>T
MANE Select: NM_004168
dbSNP: rs35277230
Type: single nucleotide variant
Location: chr5:235249 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.06 · 5 PDB
Residue 390: an α-helix

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

Disease context

neurodegeneration with ataxia and late-onset optic atrophy — 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 mitochondrial complex II deficiency, nuclear type 1

Similar variants

SDHA p.Phe390Leu 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
SDHA c.1261-1G>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-phe390 (accessed [today's date]).

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