Is COX19 p.His42Arg (c.125A>G) pathogenic?

COX19 p.His42Arg (c.125A>G) is classified Likely benign in COX19 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-12). AlphaMissense: likely benign (0.0492); Ultra-rare (popmax 0.0541%, eas).

How common is COX19 p.His42Arg (c.125A>G) in the general population?

COX19 p.His42Arg (c.125A>G) is ultra-rare (popmax 0.0541%, eas) (gnomAD).

What do computational predictors say about COX19 p.His42Arg (c.125A>G)?

AlphaMissense predicts likely benign (score 0.0492) — an in-silico prediction, not a clinical call.

COX19 p.His42Arg

c.125A>G · VCV4233004

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0492 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0541%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0492	likely benign
REVEL	0.086	moderately benign-leaning
SaProt	LLR -4.35	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 0.48	GERP 3.2, phastCons 0.061
Regional constraint	o/e 1.25	unconstrained · MANE · 6,128 bp · p 0.0099 · regional, not allelic
Overall
CADD	6.814	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 0.0541% East Asian · 24/44,394 alleles

Filtering AF 0.0372% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0316%

Overall 0.00181% 29/1,601,154 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0541%	1,850
Remaining individualsnot grpmax-eligible	0.00161%	62,008
European (non-Finnish)	0.00034%	293,824

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: COX19
Protein: p.His42Arg
Coding: c.125A>G
MANE Select: NM_001031617
Type: single nucleotide variant
Location: chr7:973250 (GRCh38)
Gene constraint: LOEUF 1.911 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.23
Residue 42: the chch domain; a disulfide bond

Full COX19 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COX19 p.Ala49Gly Uncertain significance ★ ⚠ same type
COX19 p.Asn43Lys Uncertain significance ★ ⚠ same type
COX19 p.Asn44Ser Uncertain significance ★ ⚠ same type
COX19 p.Asn6Ser Uncertain significance ★ ⚠ same type
COX19 p.Asp25His Uncertain significance ★ ⚠ same type
COX19 p.Asp25Tyr Uncertain significance ★ ⚠ same type
COX19 p.Cys40Arg Uncertain significance ★ ⚠ same type
COX19 p.Glu60Gln 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/cox19-p-his42arg (accessed [today's date]).

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