Is SERAC1 p.Pro199= (c.597A>G) pathogenic?

SERAC1 p.Pro199= (c.597A>G) is classified Benign in SERAC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-21). Rare (popmax 0.761%, eas); Associated with 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome.

How common is SERAC1 p.Pro199= (c.597A>G) in the general population?

SERAC1 p.Pro199= (c.597A>G) is rare (popmax 0.761%, eas) (gnomAD).

How is MEGDEL syndrome inherited?

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

SERAC1 p.Pro199=

Q: What condition is associated with SERAC1 p.Pro199= (c.597A>G)?

SERAC1 p.Pro199= (c.597A>G) is associated with 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome (ClinVar).

c.597A>G · VCV3643784

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.761%, 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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.5	GERP -3.1
Overall
CADD	5.889	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.761% East Asian · 341/44,814 alleles

Filtering AF 0.694% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.668%

Overall 0.0216% 348/1,610,782 alleles · rare exomes 336/1,458,480 · genomes 12/152,302 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.761%	131
Remaining individualsnot grpmax-eligible	0.0112%	8,916

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.Pro199=
Coding: c.597A>G
MANE Select: NM_032861
Type: single nucleotide variant
Location: chr6:158144311 (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 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
SERAC1 p.Ser498Thr Pathogenic/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/serac1-p-pro199 (accessed [today's date]).

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