Is CORO2A p.Phe40Leu (c.120C>G) pathogenic?

CORO2A p.Phe40Leu (c.120C>G) is classified Uncertain significance in CORO2A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-26). AlphaMissense: likely pathogenic (0.8252); Very rare (popmax 0.000763%, nfe).

How common is CORO2A p.Phe40Leu (c.120C>G) in the general population?

CORO2A p.Phe40Leu (c.120C>G) is very rare (popmax 0.000763%, nfe) (gnomAD).

What do computational predictors say about CORO2A p.Phe40Leu (c.120C>G)?

AlphaMissense predicts likely pathogenic (score 0.8252) — an in-silico prediction, not a clinical call.

CORO2A p.Phe40Leu

c.120C>G · rs1393098252 · VCV2541046

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8252 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000763%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8252	likely pathogenic
REVEL	0.383	indeterminate
SaProt	LLR -8.89	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 33 kb · p 0.0046 · regional, not allelic
Overall
CADD	24.8	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 0.000763% European (non-Finnish) · 9/1,180,050 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000558% 9/1,614,124 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: CORO2A
Protein: p.Phe40Leu
Coding: c.120C>G
MANE Select: NM_052820
dbSNP: rs1393098252
Type: single nucleotide variant
Location: chr9:98157541 (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-phe40leu (accessed [today's date]).

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