Is COPS7B p.Arg263His (c.788G>A) pathogenic?

COPS7B p.Arg263His (c.788G>A) is classified Uncertain significance in COPS7B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-28). AlphaMissense: likely benign (0.3084); Very rare (popmax 0.00119%, sas).

How common is COPS7B p.Arg263His (c.788G>A) in the general population?

COPS7B p.Arg263His (c.788G>A) is very rare (popmax 0.00119%, sas) (gnomAD).

What do computational predictors say about COPS7B p.Arg263His (c.788G>A)?

AlphaMissense predicts likely benign (score 0.3084) — an in-silico prediction, not a clinical call.

COPS7B p.Arg263His

c.788G>A · VCV3496008

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3084 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00119%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3084	likely benign
REVEL	0.163	moderately benign-leaning
SaProt	LLR -8.05	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 8.6	GERP 0.86, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 19 kb · p 2e-05 · regional, not allelic
Overall
CADD	28.1	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 0.00119% South Asian · 1/84,066 alleles

Filtering AF 0.000514% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000376%

Overall 0.000774% 12/1,550,776 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00119%	84,066
European (non-Finnish)	0.000959%	104,304

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: COPS7B
Protein: p.Arg263His
Coding: c.788G>A
MANE Select: NM_022730
Type: single nucleotide variant
Location: chr2:231807638 (GRCh38)
Gene constraint: LOEUF 0.517 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 85.00 · 25 PDB
Residue 263: a modified residue (phosphoserine); the 'disordered' region

Full COPS7B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COPS7B p.Ala222Pro Uncertain significance ★ ⚠ same type
COPS7B p.Ala244Thr Uncertain significance ★ ⚠ same type
COPS7B p.Ala29Thr Uncertain significance ★ ⚠ same type
COPS7B p.Arg160Cys Uncertain significance ★ ⚠ same type
COPS7B p.Arg160His Uncertain significance ★ ⚠ same type
COPS7B p.Arg163Gly Uncertain significance ★ ⚠ same type
COPS7B p.Asn215Ile Uncertain significance ★ ⚠ same type
COPS7B p.Asn81Ile 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/cops7b-p-arg263his (accessed [today's date]).

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