Is COX5B p.Arg112Gln (c.335G>A) pathogenic?

COX5B p.Arg112Gln (c.335G>A) is classified Uncertain significance in COX5B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-05). AlphaMissense: likely benign (0.2427); Very rare (popmax 0.0044%, sas).

How common is COX5B p.Arg112Gln (c.335G>A) in the general population?

COX5B p.Arg112Gln (c.335G>A) is very rare (popmax 0.0044%, sas) (gnomAD).

What do computational predictors say about COX5B p.Arg112Gln (c.335G>A)?

AlphaMissense predicts likely benign (score 0.2427) — an in-silico prediction, not a clinical call.

COX5B p.Arg112Gln

c.335G>A · rs746587601 · VCV2556527

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2427 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0044%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2427	likely benign
REVEL	0.765	pathogenic-leaning
SaProt	LLR -12.51	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 2,018 bp · p 0.55 · regional, not allelic
Overall
CADD	25.1	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 0.0044% South Asian · 4/90,960 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000892%

Overall 0.000682% 11/1,613,460 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0044%	22,740
East Asian	0.00223%	44,844
Admixed American	0.00167%	59,840
European (non-Finnish)	0.000424%	235,965

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: COX5B
Protein: p.Arg112Gln
Coding: c.335G>A
MANE Select: NM_001862
dbSNP: rs746587601
Type: single nucleotide variant
Location: chr2:97648053 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI 0.50 (gnomAD)
Structure: AlphaFold pLDDT 85.75 · 3 PDB

Full COX5B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COX5B c.278-1G>A Uncertain significance ★ same type
COX5B p.Ala54Val Uncertain significance ★ ⚠ same type
COX5B p.Arg29Cys Uncertain significance ★ ⚠ same type
COX5B p.Arg4Ser Uncertain significance ★ ⚠ same type
COX5B p.Arg7Cys Uncertain significance ★ ⚠ same type
COX5B p.Glu109Lys Uncertain significance ★ ⚠ same type
COX5B p.Gly10Ala Uncertain significance ★ ⚠ same type
COX5B p.Gly10Arg 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/cox5b-p-arg112gln (accessed [today's date]).

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