Is COX20 p.Pro108Ser (c.322C>T) pathogenic?

COX20 p.Pro108Ser (c.322C>T) is classified Uncertain significance in COX20 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-03). AlphaMissense: likely benign (0.2551); Very rare (popmax 0.00684%, eas).

How common is COX20 p.Pro108Ser (c.322C>T) in the general population?

COX20 p.Pro108Ser (c.322C>T) is very rare (popmax 0.00684%, eas) (gnomAD).

What do computational predictors say about COX20 p.Pro108Ser (c.322C>T)?

AlphaMissense predicts likely benign (score 0.2551) — an in-silico prediction, not a clinical call.

COX20 p.Pro108Ser

c.322C>T · rs1477103215 · VCV1935605

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2551 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00684%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2551	likely benign
REVEL	0.203	benign-leaning
SaProt	LLR -6.78	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 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 7,458 bp · p 0.56 · regional, not allelic
Overall
CADD	26.1	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

Grpmax group 0.00684% East Asian · 3/43,886 alleles

Filtering AF 0.00181% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000902%

Overall 0.000208% 3/1,441,100 alleles · very rare

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: COX20
Protein: p.Pro108Ser
Coding: c.322C>T
MANE Select: NM_198076
dbSNP: rs1477103215
Type: single nucleotide variant
Location: chr1:244843141 (GRCh38)
Gene constraint: LOEUF 1.927 · pLI 0.06 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 66.42

Full COX20 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COX20 p.Pro108Leu Uncertain significance ★ ⚠ same residue
COX20 p.Pro108fs Uncertain significance ★ same residue
COX20 c.157+3G>C Pathogenic/Likely pathogenic ★★ same type
COX20 p.Lys14Arg Pathogenic ★★ ⚠ same type
COX20 p.Tyr36Ter Likely pathogenic ★★ same type
COX20 p.Ala3Thr Uncertain significance ★★ ⚠ same type
COX20 p.Arg31Trp Uncertain significance ★★ ⚠ same type
COX20 p.Arg54Gly 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/cox20-p-pro108ser (accessed [today's date]).

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