Is COX14 p.Arg33Gln (c.98G>A) pathogenic?

COX14 p.Arg33Gln (c.98G>A) is classified Uncertain significance in COX14 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-16). AlphaMissense: likely benign (0.0986); Ultra-rare (popmax 0.045%, sas).

How common is COX14 p.Arg33Gln (c.98G>A) in the general population?

COX14 p.Arg33Gln (c.98G>A) is ultra-rare (popmax 0.045%, sas) (gnomAD).

What do computational predictors say about COX14 p.Arg33Gln (c.98G>A)?

AlphaMissense predicts likely benign (score 0.0986) — an in-silico prediction, not a clinical call.

COX14 p.Arg33Gln

c.98G>A · rs368516862 · VCV2465198

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0986 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.045%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0986	likely benign
REVEL	0.574	indeterminate
SaProt	LLR -5.09	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP -0.27, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 170 bp · p 0.99 · regional, not allelic
Overall
CADD	22.5	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 0.045% South Asian · 41/91,082 alleles

Filtering AF 0.034% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0302%

Overall 0.00539% 87/1,614,128 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.045%	2,222
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0048%	20,837
European (non-Finnish)	0.00347%	28,780
African / African-American	0.00133%	75,036

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: COX14
Protein: p.Arg33Gln
Coding: c.98G>A
MANE Select: NM_032901
dbSNP: rs368516862
Type: single nucleotide variant
Location: chr12:50120141 (GRCh38)
Gene constraint: LOEUF 1.203 · pLI 0.22 (gnomAD)
Structure: AlphaFold pLDDT 86.03

Full COX14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COX14 p.Arg41Cys Uncertain significance ★★ ⚠ same type
COX14 p.Met1Ile Uncertain significance ★★ same type
COX14 p.Ser54Pro Uncertain significance ★★ ⚠ same type
COX14 p.Thr3Ala Uncertain significance ★★ ⚠ same type
COX14 p.Tyr25Cys Uncertain significance ★★ ⚠ same type
COX14 c.-8-132C>T Benign ★★ same type
COX14 c.-8-14A>G Likely benign ★★ same type
COX14 c.-8-1526G>A Benign ★★ 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/cox14-p-arg33gln (accessed [today's date]).

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