Is COQ8B p.Ala487Ser (c.1459G>T) pathogenic?

COQ8B p.Ala487Ser (c.1459G>T) is classified Uncertain significance in COQ8B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-12). AlphaMissense: likely benign (0.102); Absent from gnomAD v4.1; Associated with nephrotic syndrome, type 9.

What condition is associated with COQ8B p.Ala487Ser (c.1459G>T)?

COQ8B p.Ala487Ser (c.1459G>T) is associated with nephrotic syndrome, type 9 (ClinVar).

How common is COQ8B p.Ala487Ser (c.1459G>T) in the general population?

COQ8B p.Ala487Ser (c.1459G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COQ8B p.Ala487Ser (c.1459G>T)?

AlphaMissense predicts likely benign (score 0.102) — an in-silico prediction, not a clinical call.

COQ8B p.Ala487Ser

Q: How is Hereditary steroid-resistant nephrotic syndrome inherited?

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

c.1459G>T · rs751280402 · VCV2688856

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.102 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

nephrotic syndrome, type 9

Computational evidence

Protein change
AlphaMissense	0.102	likely benign
REVEL	0.107	moderately benign-leaning
SaProt	LLR -2.89	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 2.6	GERP 0.5, phastCons 0.99
Regional constraint	o/e 0.89	unconstrained · MANE · 23 kb · p 0.0023 · regional, not allelic
Overall
CADD	15.82	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: COQ8B
Protein: p.Ala487Ser
Coding: c.1459G>T
MANE Select: NM_024876
dbSNP: rs751280402
Type: single nucleotide variant
Location: chr19:40692211 (GRCh38)
Gene constraint: LOEUF 0.923 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.00

Full COQ8B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

nephrotic syndrome, type 9 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary steroid-resistant nephrotic syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Adolescent, Adult, Antenatal, Childhood, Infancy, Neonatal

Similar variants

COQ8B c.1035+2T>C Pathogenic ★★ same condition
COQ8B c.367+1G>A Pathogenic/Likely pathogenic ★★ same condition
COQ8B c.893+2T>A Pathogenic/Likely pathogenic ★★ same condition
COQ8B p.Arg178Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
COQ8B p.Arg362Ter Pathogenic/Likely pathogenic ★★ same condition
COQ8B p.Arg477Gln Pathogenic/Likely pathogenic ★★ same condition
COQ8B p.Asn253Lys Likely pathogenic ★★ same condition
COQ8B p.Glu483Ter 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/coq8b-p-ala487ser (accessed [today's date]).

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