Is SERAC1 p.Pro175= (c.525G>A) pathogenic?

SERAC1 p.Pro175= (c.525G>A) is classified Likely benign in SERAC1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-30). Very rare (popmax 0.00446%, eas); Associated with 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome.

How common is SERAC1 p.Pro175= (c.525G>A) in the general population?

SERAC1 p.Pro175= (c.525G>A) is very rare (popmax 0.00446%, eas) (gnomAD).

How is MEGDEL syndrome inherited?

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

SERAC1 p.Pro175=

Q: What condition is associated with SERAC1 p.Pro175= (c.525G>A)?

SERAC1 p.Pro175= (c.525G>A) is associated with 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome (ClinVar).

c.525G>A · rs774652383 · VCV760807

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Conditions

3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -4.4	GERP -3.4
Overall
CADD	9.413	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,830 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.000496% 8/1,612,952 alleles · very rare exomes 8/1,460,726 · genomes 0/152,226 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,415
Remaining individualsnot grpmax-eligible	0.0016%	62,476
European (non-Finnish)	0.000424%	235,856

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: SERAC1
Protein: p.Pro175=
Coding: c.525G>A
MANE Select: NM_032861
dbSNP: rs774652383
Type: single nucleotide variant
Location: chr6:158144383 (GRCh38)
Gene constraint: LOEUF 0.681 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.66

Full SERAC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For MEGDEL syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

SERAC1 p.Pro175Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
SERAC1 c.1403+1G>C Pathogenic ★★ same condition
SERAC1 p.Arg148Ter Pathogenic ★★ same condition
SERAC1 p.Arg368Ter Pathogenic ★★ same condition
SERAC1 p.Arg387Ter Pathogenic/Likely pathogenic ★★ same condition
SERAC1 p.Arg447Ter Pathogenic ★★ same condition
SERAC1 p.Arg68Ter Pathogenic/Likely pathogenic ★★ same condition
SERAC1 p.Gln376Ter 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/serac1-p-pro175 (accessed [today's date]).

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