Is CORO2B p.Arg464Trp (c.1390C>T) pathogenic?

CORO2B p.Arg464Trp (c.1390C>T) is classified Uncertain significance in CORO2B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-20). AlphaMissense: likely benign (0.1888); Very rare (popmax 0.00801%, afr).

How common is CORO2B p.Arg464Trp (c.1390C>T) in the general population?

CORO2B p.Arg464Trp (c.1390C>T) is very rare (popmax 0.00801%, afr) (gnomAD).

What do computational predictors say about CORO2B p.Arg464Trp (c.1390C>T)?

AlphaMissense predicts likely benign (score 0.1888) — an in-silico prediction, not a clinical call.

CORO2B p.Arg464Trp

c.1390C>T · rs146678597 · VCV3076400

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1888 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1888	likely benign
REVEL	0.325	indeterminate
SaProt	LLR -10.27	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP -2.5, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 6,534 bp · p 0.56 · regional, not allelic
Overall
CADD	29.4	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 0.00801% African / African-American · 6/74,914 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.0013% 21/1,613,926 alleles · very rare exomes 16/1,461,772 · genomes 5/152,154 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,486
Remaining individualsnot grpmax-eligible	0.0032%	31,243
Admixed American	0.00167%	59,976
South Asian	0.0011%	91,068
European (non-Finnish)	0.000932%	107,276

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: CORO2B
Protein: p.Arg464Trp
Coding: c.1390C>T
MANE Select: NM_006091
dbSNP: rs146678597
Type: single nucleotide variant
Location: chr15:68725921 (GRCh38)
Gene constraint: LOEUF 0.633 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 91.58

Full CORO2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CORO2B p.Arg464Gln Uncertain significance ★ ⚠ same residue
CORO2B p.Ala334Val Uncertain significance ★ ⚠ same type
CORO2B p.Ala60Thr Uncertain significance ★ ⚠ same type
CORO2B p.Arg124Gln Uncertain significance ★ ⚠ same type
CORO2B p.Arg13His Uncertain significance ★ ⚠ same type
CORO2B p.Arg213His Uncertain significance ★ ⚠ same type
CORO2B p.Arg227Gln Uncertain significance ★ same type
CORO2B p.Arg236Gln 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/coro2b-p-arg464trp (accessed [today's date]).

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