Is COX6A2 p.Ser85Asn (c.254G>A) pathogenic?

COX6A2 p.Ser85Asn (c.254G>A) is classified Uncertain significance in COX6A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-14). AlphaMissense: likely benign (0.1868); Absent from gnomAD v4.1.

How common is COX6A2 p.Ser85Asn (c.254G>A) in the general population?

COX6A2 p.Ser85Asn (c.254G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COX6A2 p.Ser85Asn (c.254G>A)?

AlphaMissense predicts likely benign (score 0.1868) — an in-silico prediction, not a clinical call.

COX6A2 p.Ser85Asn

c.254G>A · rs1442358571 · VCV2284372

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1868 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,413,936)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1868	likely benign
REVEL	0.162	moderately benign-leaning
SaProt	LLR -8.25	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 8.3	GERP -0.39, phastCons 1
Regional constraint	o/e 1.26	unconstrained · MANE · 548 bp · p 0.002 · regional, not allelic
Overall
CADD	17.68	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

No allele count reported in gnomAD v4.1 (AN 1,413,936). 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: COX6A2
Protein: p.Ser85Asn
Coding: c.254G>A
MANE Select: NM_005205
dbSNP: rs1442358571
Type: single nucleotide variant
Location: chr16:31427814 (GRCh38)
Gene constraint: LOEUF 1.913 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.30

Full COX6A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COX6A2 p.Ser85= Likely benign same residue
COX6A2 p.Leu81Val Uncertain significance ★★ ⚠ same type
COX6A2 p.Ser39Arg Likely pathogenic ★ ⚠ same type
COX6A2 p.Ala2Thr Uncertain significance ★ ⚠ same type
COX6A2 p.Arg54Leu Uncertain significance ★ ⚠ same type
COX6A2 p.Arg60Cys Uncertain significance ★ ⚠ same type
COX6A2 p.Arg66Gly Uncertain significance ★ ⚠ same type
COX6A2 p.Arg68His Uncertain significance ★ ⚠ same type

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/cox6a2-p-ser85asn (accessed [today's date]).

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