Is SERAC1 p.Arg306Gln (c.917G>A) pathogenic?

SERAC1 p.Arg306Gln (c.917G>A) is classified Benign/Likely benign in SERAC1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-12-19). AlphaMissense: likely benign (0.0602); Rare (popmax 0.744%, afr); Associated with 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome.

How common is SERAC1 p.Arg306Gln (c.917G>A) in the general population?

SERAC1 p.Arg306Gln (c.917G>A) is rare (popmax 0.744%, afr) (gnomAD).

How is MEGDEL syndrome inherited?

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

What do computational predictors say about SERAC1 p.Arg306Gln (c.917G>A)?

AlphaMissense predicts likely benign (score 0.0602) — an in-silico prediction, not a clinical call.

SERAC1 p.Arg306Gln

Q: What condition is associated with SERAC1 p.Arg306Gln (c.917G>A)?

SERAC1 p.Arg306Gln (c.917G>A) is associated with 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome (ClinVar).

c.917G>A · rs114943513 · VCV379604

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0602 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.744%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

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

Computational evidence

Protein change
AlphaMissense	0.0602	likely benign
REVEL	0.13	moderately benign-leaning
SaProt	LLR -5.36	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.11	GERP -2.2, phastCons 0.014
Regional constraint	o/e 0.79	unconstrained · MANE · 47 kb · p 3.1e-09 · regional, not allelic
Overall
CADD	0.335	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.744% African / African-American · 558/75,016 alleles

Filtering AF 0.693% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.673%

Overall 0.0444% 717/1,614,118 alleles · rare exomes 358/1,461,826 · genomes 359/152,292 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.744%	134
Admixed American	0.138%	723
Remaining individualsnot grpmax-eligible	0.0512%	1,953
Middle Eastern	0.0495%	2,021
South Asian	0.0209%	4,794
East Asian	0.0134%	7,480
European (non-Finnish)	0.00136%	73,750

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.Arg306Gln
Coding: c.917G>A
MANE Select: NM_032861
dbSNP: rs114943513
Type: single nucleotide variant
Location: chr6:158128206 (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.Arg306Ter 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-arg306gln (accessed [today's date]).

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