Is CORO2B p.Met260Leu (c.778A>C) pathogenic?

CORO2B p.Met260Leu (c.778A>C) is classified Uncertain significance in CORO2B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-21). AlphaMissense: likely benign (0.0823); Very rare (popmax 0.000424%, nfe).

How common is CORO2B p.Met260Leu (c.778A>C) in the general population?

CORO2B p.Met260Leu (c.778A>C) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about CORO2B p.Met260Leu (c.778A>C)?

AlphaMissense predicts likely benign (score 0.0823) — an in-silico prediction, not a clinical call.

CORO2B p.Met260Leu

c.778A>C · VCV4232951

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0823 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0823	likely benign
REVEL	0.278	benign-leaning
SaProt	LLR -5.51	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 7	GERP -0.4, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 140 kb · p 2.5e-16 · 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 0.000424% European (non-Finnish) · 5/1,179,770 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000342% 5/1,461,588 alleles · very rare

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.Met260Leu
Coding: c.778A>C
MANE Select: NM_006091
Type: single nucleotide variant
Location: chr15:68714571 (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.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
CORO2B p.Arg244Thr 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-met260leu (accessed [today's date]).

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