Is CORO2A p.Arg33Cys (c.97C>T) pathogenic?

CORO2A p.Arg33Cys (c.97C>T) is classified Uncertain significance in CORO2A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-20). AlphaMissense: likely benign (0.0761); Very rare (popmax 0.00415%, nfe).

How common is CORO2A p.Arg33Cys (c.97C>T) in the general population?

CORO2A p.Arg33Cys (c.97C>T) is very rare (popmax 0.00415%, nfe) (gnomAD).

What do computational predictors say about CORO2A p.Arg33Cys (c.97C>T)?

AlphaMissense predicts likely benign (score 0.0761) — an in-silico prediction, not a clinical call.

CORO2A p.Arg33Cys

c.97C>T · rs770982762 · VCV3076395

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0761 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00415%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0761	likely benign
REVEL	0.24	benign-leaning
SaProt	LLR -10.62	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP -0.32, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 33 kb · p 0.0046 · regional, not allelic
Overall
CADD	20.8	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 0.00415% European (non-Finnish) · 49/1,180,046 alleles

Filtering AF 0.00318% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00286%

Overall 0.00341% 55/1,614,082 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00415%	24,083
Remaining individualsnot grpmax-eligible	0.0032%	31,241
South Asian	0.0022%	45,543
Finnishnot grpmax-eligible	0.00156%	64,030
African / African-American	0.00133%	74,934

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: CORO2A
Protein: p.Arg33Cys
Coding: c.97C>T
MANE Select: NM_052820
dbSNP: rs770982762
Type: single nucleotide variant
Location: chr9:98157564 (GRCh38)
Gene constraint: LOEUF 0.902 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.12

Full CORO2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CORO2A p.Ala105Asp Uncertain significance ★ ⚠ same type
CORO2A p.Ala132Thr Uncertain significance ★ ⚠ same type
CORO2A p.Ala144Thr Uncertain significance ★ ⚠ same type
CORO2A p.Ala145Thr Uncertain significance ★ ⚠ same type
CORO2A p.Ala218Thr Uncertain significance ★ ⚠ same type
CORO2A p.Ala280Thr Uncertain significance ★ ⚠ same type
CORO2A p.Ala59Ser Uncertain significance ★ ⚠ same type
CORO2A p.Ala59Thr 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/coro2a-p-arg33cys (accessed [today's date]).

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