Is SERAC1 p.Pro618fs (c.1850_1851insA) pathogenic?

SERAC1 p.Pro618fs (c.18501851insA) is classified Pathogenic in SERAC1 (ClinVar, No assertion criteria, 1 submitter). No gnomAD frequency available for this variant; Associated with 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome.

What condition is associated with SERAC1 p.Pro618fs (c.1850_1851insA)?

SERAC1 p.Pro618fs (c.1850_1851insA) is associated with 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome (ClinVar).

How common is SERAC1 p.Pro618fs (c.1850_1851insA) in the general population?

SERAC1 p.Pro618fs (c.1850_1851insA) is no gnomAD frequency available for this variant (gnomAD).

How is MEGDEL syndrome inherited?

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

SERAC1 p.Pro618fs

c.1850_1851insA · rs2128409409 · VCV1184550

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (17 of 17) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.8	GERP -2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SERAC1
Protein: p.Pro618fs
Coding: c.1850_1851insA
MANE Select: NM_032861
dbSNP: rs2128409409
Type: Insertion
Location: chr6:158111480 (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.1167_1170del Pathogenic/Likely pathogenic ★★ same condition
SERAC1 c.1403+1G>C Pathogenic ★★ same condition
SERAC1 c.1822_1828+10delinsACCAACAGG Pathogenic/Likely pathogenic ★★ same condition
SERAC1 p.Ala609fs Pathogenic/Likely pathogenic ★★ same condition
SERAC1 p.Arg103fs Pathogenic/Likely pathogenic ★★ same condition
SERAC1 p.Arg148Ter Pathogenic ★★ same condition
SERAC1 p.Arg368Ter Pathogenic ★★ same condition
SERAC1 p.Arg387Ter 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-pro618fs (accessed [today's date]).

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